Structural insight into the cooperativity of spin crossover compounds.

Spin-crossover (SCO) compounds are promising materials for a wide variety of industrial applications. However, the fundamental understanding of their nature of transition and its effect on the physical properties are still being fervently explored; the microscopic knowledge of their transition is essential for tailoring their properties. Here an attempt is made to correlate the changes in macroscopic physical properties with microscopic structural changes in the orthorhombic and monoclinic polymorphs of the SCO compound Fe(PM-Bia)2(NCS)2 (PM = N-2'-pyridylmethylene and Bia = 4-aminobiphenyl) by employing single-crystal X-ray diffraction, magnetization and DSC measurements. The dependence of macroscopic properties on cooperativity, highlighting the role of hydrogen bonding, π-π and van der Waals interactions is discussed. Values of entropy, enthalpy and cooperativity are calculated numerically based on the Slichter-Drickamer model. The particle size dependence of the magnetic properties is probed along with the thermal exchange and the kinetic behavior of the two polymorphs based on the dependence of magnetization on temperature scan rate and a theoretical model is proposed for the calculation of the non-equilibrium spin-phase fraction. Also a scan-rate-dependent two-step behavior observed for the orthorhombic polymorph, which is absent for the monoclinic polymorph, is reported. Moreover, it is found that the radiation dose from synchrotron radiation affects the spin-crossover process and shifts the transition region to lower temperatures, implying that the spin crossover can be tuned with radiation damage.

Proposed domains for assessing postpartum recovery: a concept elicitation study.

OBJECTIVE: To propose postpartum recovery domains. DESIGN: Concept elicitation study. SETTING: Semi-structured interviews. POPULATION: Ten writing committee members and 50 stakeholder interviews (23 postpartum women, nine general obstetricians, five maternal and fetal medicine specialists, eight nurses and five obstetric anaesthetists). METHODS: Alternating interviews and focus group meetings until concept saturation was achieved (no new themes discussed in three consecutive interviews). Interviews were digitally recorded and transcribed, and an iterative coding process was used to identify domains. MAIN OUTCOME MEASURES: The primary outcome was to identify recovery domains. We also report key symptoms and concerns. Discussion frequency and importance scores (0-100; 0 = not important; 100 = vitally important to recovery) were used to rank domains. Discussion frequency was used to rank factors helping and hindering recovery, and to determine the greatest challenges experienced postpartum. RESULTS: Thirty-four interviews and two focus group meetings were performed. The 13 postpartum recovery domains identified, (ranked highest to lowest) were: psychosocial distress, surgical/medical factors, infant feeding and breast health, psychosocial support, pain, physical function, sleep, motherhood experience, infant health, fatigue, appearance, sexual function and cognition. The most frequently discussed factors facilitating postpartum recovery were: family support, lactation/breastfeeding support and partner support. The most frequently discussed factor hindering recovery was inadequate social support. The most frequent challenges reported were: breastfeeding (week 1), breastfeeding (week 3) and sleep (week 6). CONCLUSIONS: We propose 13 domains that comprehensively describe recovery in women delivering in a single centre within the USA. This provides a novel framework to study the postpartum recovery process. TWEETABLE ABSTRACT: We propose 13 postpartum recovery domains that provide a framework to study the recovery process following childbirth.

Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry.

Exposure to microgravity (µG) during space flights produces a state of immunosuppression, leading to increased viral shedding, which could interfere with long term missions. However, the cellular mechanisms that underlie the immunosuppressive effects of µG are ill-defined. A deep understanding of human immune adaptations to µG is a necessary first step to design data-driven interventions aimed at preserving astronauts' immune defense during short- and long-term spaceflights. We employed a high-dimensional mass cytometry approach to characterize over 250 cell-specific functional responses in 18 innate and adaptive immune cell subsets exposed to 1G or simulated (s)µG using the Rotating Wall Vessel. A statistically stringent elastic net method produced a multivariate model that accurately stratified immune responses observed in 1G and sµG (p value 2E-4, cross-validation). Aspects of our analysis resonated with prior knowledge of human immune adaptations to µG, including the dampening of Natural Killer, CD4+ and CD8+ T cell responses. Remarkably, we found that sµG enhanced STAT5 signaling responses of immunosuppressive Tregs. Our results suggest µG exerts a dual effect on the human immune system, simultaneously dampening cytotoxic responses while enhancing Treg function. Our study provides a single-cell readout of sµG-induced immune dysfunctions and an analytical framework for future studies of human immune adaptations to human long-term spaceflights.

Systemic Immunologic Consequences of Chronic Periodontitis.

Chronic periodontitis (ChP) is a prevalent inflammatory disease affecting 46% of the US population. ChP produces a profound local inflammatory response to dysbiotic oral microbiota that leads to destruction of alveolar bone and tooth loss. ChP is also associated with systemic illnesses, including cardiovascular diseases, malignancies, and adverse pregnancy outcomes. However, the mechanisms underlying these adverse health outcomes are poorly understood. In this prospective cohort study, we used a highly multiplex mass cytometry immunoassay to perform an in-depth analysis of the systemic consequences of ChP in patients before (n = 28) and after (n = 16) periodontal treatment. A high-dimensional analysis of intracellular signaling networks revealed immune system-wide dysfunctions differentiating patients with ChP from healthy controls. Notably, we observed exaggerated proinflammatory responses to Porphyromonas gingivalis-derived lipopolysaccharide in circulating neutrophils and monocytes from patients with ChP. Simultaneously, natural killer cell responses to inflammatory cytokines were attenuated. Importantly, the immune alterations associated with ChP were no longer detectable 3 wk after periodontal treatment. Our findings demarcate systemic and cell-specific immune dysfunctions in patients with ChP, which can be temporarily reversed by the local treatment of ChP. Future studies in larger cohorts are needed to test the boundaries of generalizability of our results.

Analgesic and sympatholytic effects of low-dose intrathecal clonidine compared with bupivacaine: a dose-response study in female volunteers.

BACKGROUND: A wide range of doses has been suggested for intrathecal clonidine, but no dose-ranging study has examined analgesic effects below 100 µg. The primary aim of this volunteer study was to assess the dose vs analgesic effect relationship for doses of intrathecal clonidine below 100 µg. METHODS: After IRB approval and signed informed consent, 11 healthy female volunteers participated in this randomized, double-blinded, cross-over study using a dose-ranging sparse-sampling technique. Participants received intrathecal clonidine (doses 0-100 µg; n=10) and intrathecal bupivacaine (doses 0-8.8 mg; n=9) on separate study days. At baseline, 30, and 60 min from drug administration, experimental heat pain tolerance was assessed at both a lumbar and a cranial dermatome. Heat and cold perception thresholds were assessed at the same time intervals. Heart rate (HR), arterial pressure, and forearm-finger and toe-leg cutaneous temperature gradients (Tfinger-arm and Ttoe-leg) were used as measures of sympatholysis. RESULTS: Both intrathecal clonidine and bupivacaine caused significant, dose-dependent analgesic effects at the leg but not the head. Significant analgesia to experimental heat pain was detected above 25 µg clonidine and 3 mg bupivacaine. Administration of bupivacaine but not clonidine resulted in a significant dose-related decrease in HR and Ttoe-leg; neither drug caused dose-related sympatholytic effects in the doses used. CONCLUSIONS: After 50 µg clonidine or 5 mg bupivacaine, the heat pain tolerance increased by ∼1°C, similar to the analgesic effect of 5 mg epidural morphine or 30 µg epidural fentanyl in previous studies using this experimental heat pain model. Our results provide additional data for rational dose selection of intrathecal clonidine.

Dielectric properties of charge-ordered LuFe(2)O(4) revisited: the apparent influence of contacts.

We show results of broadband dielectric measurements on the charge ordered, proposed to be multiferroic material LuFe(2)O(4). The temperature and frequency dependence of the complex permittivity as investigated for temperatures above and below the charge-order transition near T(CO)≈320 K and for frequencies up to 1 GHz can be well described by a standard equivalent-circuit model considering Maxwell-Wagner-type contacts and hopping induced ac conductivity. No pronounced contribution of intrinsic dipolar polarization could be found, and thus the ferroelectric character of the charge order in LuFe(2)O(4) has to be questioned.

Charge order in LuFe2O4: an unlikely route to ferroelectricity.

We present the refinement of the crystal structure of charge-ordered LuFe2O4, based on single-crystal x-ray diffraction data. The arrangement of the different Fe-valence states, determined with bond-valence-sum analysis, corresponds to a stacking of charged Fe bilayers, in contrast with the polar bilayers previously suggested. This arrangement is supported by an analysis of x-ray magnetic circular dichroism spectra, which also evidences a strong charge-spin coupling. The nonpolar bilayers are inconsistent with charge order based ferroelectricity.

Competing ferri- and antiferromagnetic phases in geometrically frustrated LuFe2O4.

We present a detailed study of magnetism in LuFe(2)O(4), combining magnetization measurements with neutron and soft x-ray diffraction. The magnetic phase diagram in the vicinity of T(N) involves a metamagnetic transition separating an antiferro- and a ferrimagnetic phase. For both phases the spin structure is refined by neutron diffraction. Observed diffuse magnetic scattering far above T(N) is explained in terms of near degeneracy of the magnetic phases.

Intact neurobehavioral development and dramatic impairments of procedural-like memory following neonatal ventral hippocampal lesion in rats.

Neonatal ventral hippocampal lesions (NVHL) in rats are considered a potent developmental model of schizophrenia. After NVHL, rats appear normal during their preadolescent time, whereas in early adulthood, they develop behavioral deficits paralleling symptomatic aspects of schizophrenia, including hyperactivity, hypersensitivity to amphetamine (AMPH), prepulse and latent inhibition deficits, reduced social interactions, and spatial working and reference memory alterations. Surprisingly, the question of the consequences of NVHL on postnatal neurobehavioral development has not been addressed. This is of particular importance, as a defective neurobehavioral development could contribute to impairments seen in adult rats. Therefore, at several time points of the early postsurgical life of NVHL rats, we assessed behaviors accounting for neurobehavioral development, including negative geotaxis and grip strength (PD11), locomotor coordination (PD21), and open-field (PD25). At adulthood, the rats were tested for anxiety levels, locomotor activity, as well as spatial reference memory performance. Using a novel task, we also investigated the consequences of the lesions on procedural-like memory, which had never been tested following NVHL. Our results point to preserved neurobehavioral development. They also confirm the already documented locomotor hyperactivity, spatial reference memory impairment, and hyperresponsiveness to AMPH. Finally, our rseults show for the first time that NVHL disabled the development of behavioral routines, suggesting dramatic procedural memory deficits. The presence of procedural memory deficits in adult rats subjected to NHVL suggests that the lesions lead to a wider range of cognitive deficits than previously shown. Interestingly, procedural or implicit memory impairments have also been reported in schizophrenic patients.

The analgesic and antihyperalgesic effects of transcranial electrostimulation with combined direct and alternating current in healthy volunteers.

BACKGROUND: Transcranial electrostimulation (TES) has been reported to produce clinically significant analgesia, but randomized and double-blind studies are lacking. We investigated the analgesic and antihyperalgesic effects of TES in validated human experimental pain models. METHODS: In 20 healthy male subjects we evaluated the analgesic and antihyperalgesic effects of TES(60Hz) and TES(100Hz) to heat and mechanical pain in experimentally induced ultraviolet B skin sunburns and in normal skin. Previous animal studies in our laboratory predicted that TES(60Hz) would provide significant analgesia, and TES(100Hz) was a suitable active control. The study was conducted in a double-blind, randomized, 2-way cross-over fashion. TES was administered for 35 minutes. Quantitative sensory testing evaluating heat and mechanical pain thresholds was conducted before TES, during TES, and 45 minutes after TES. RESULTS: TES (TES(60Hz) > TES(100Hz)) evoked rapidly developing, significant thermal and mechanical antihyperalgesic effects in the ultraviolet B lesion, and attenuated thermal pain in unimpaired skin. No long-lasting analgesic and antihyperalgesic effects of a single TES treatment were demonstrated in this study. CONCLUSIONS: TES produces significant, frequency-dependent antihyperalgesic and analgesic effects in humans. The characteristics of the TES effects indicate a high likelihood of its ability to modulate both peripheral sensitization of nociceptors and central hyperexcitability.

Imaging and manipulation of the competing electronic phases near the Mott metal-insulator transition.

The complex interplay between the electron and lattice degrees of freedom produces multiple nearly degenerate electronic states in correlated electron materials. The competition between these degenerate electronic states largely determines the functionalities of the system, but the invoked mechanism remains in debate. By imaging phase domains with electron microscopy and interrogating individual domains in situ via electron transport spectroscopy in double-layered Sr(3)(Ru(1-x)Mn(x))(2)O(7) (x = 0 and 0.2), we show in real-space that the microscopic phase competition and the Mott-type metal-insulator transition are extremely sensitive to applied mechanical stress. The revealed dynamic phase evolution with applied stress provides the first direct evidence for the important role of strain effect in both phase separation and Mott metal-insulator transition due to strong electron-lattice coupling in correlated systems.

Selective antagonism of opioid-induced ventilatory depression by an ampakine molecule in humans without loss of opioid analgesia.

Ventilatory depression is a significant risk associated with the use of opioids. We assessed whether opioid-induced ventilatory depression can be selectively antagonized by an ampakine without reduction of analgesia. In 16 healthy men, after a single oral dose of 1,500 mg of the ampakine CX717, a target concentration of 100 ng/ml alfentanil decreased the respiratory frequency by only 2.9 +/- 33.4% as compared with 25.6 +/- 27.9% during placebo coadministration (P < 0.01).Blood oxygenation and the ventilatory response to hypercapnic challenge also showed significantly smaller decreases with CX717 than with placebo. In contrast, CX717 did not affect alfentanil-induced analgesia in either electrical or heat-based experimental models of pain. Both ventilatory depression and analgesia were reversed with 1.6 mg of naloxone. These results support the use of ampakines as selective antidotes in humans to counter opioid-induced ventilatory depression without affecting opioid-mediated analgesia.

Charge order in LuFe2O4: antiferroelectric ground state and coupling to magnetism.

X-ray scattering by multiferroic LuFe2O4 is reported. Below 320 K, superstructure reflections indicate an incommensurate charge order with propagation close to (1/3 1/3 3/2). The corresponding charge configuration, also found by electronic structure calculations as most stable, contains polar Fe/O double layers with antiferroelectric stacking. Diffuse scattering at 360 K, with (1/3 1/3 0) propagation, indicates ferroelectric short-range correlations between neighboring double layers. The temperature dependence of the incommensuration indicates that charge order and magnetism are coupled.

Charge order, dynamics, and magnetostructural transition in multiferroic LuFe2O4.

We investigated the series of temperature and field-driven transitions in LuFe2O4 by optical and Mössbauer spectroscopies, magnetization, and x-ray scattering in order to understand the interplay between charge, structure, and magnetism in this multiferroic material. We demonstrate that charge fluctuation has an onset well below the charge ordering transition, supporting the "order by fluctuation" mechanism for the development of charge order superstructure. Bragg splitting and large magneto-optical contrast suggest a low-temperature monoclinic distortion that can be driven by both temperature and magnetic field.

Cytokine profile in human skin in response to experimental inflammation, noxious stimulation, and administration of a COX-inhibitor: a microdialysis study.

Animal studies have documented a critical role for cytokines in cell signaling events underlying inflammation and pain associated with tissue injury. While clinical reports indicate an important role of cytokines in inflammatory pain, methodological limitations have made systematic human studies difficult. This study examined the utility of a human in vivo bioassay combining microdialysis with multiplex immunoassay techniques for measuring cytokine arrays in tissue. The first experiment measured cytokines in interstitial fluid collected from non-inflamed and experimentally inflamed skin (UVB). The effects of noxious heat on cytokine release were also assessed. The second experiment examined whether anti-hyperalgesic effects of the COX-inhibitor ibuprofen were associated with decreased tissue levels of the pro-inflammatory cytokines IL-1 beta and IL-6. In the first experiment, inflammation significantly increased IL-1 beta, IL-6, IL-8, IL-10, G-CSF, and MIP-1 beta. Noxious heat but not experimental inflammation significantly increased IL-7 and IL-13. In the second experiment, an oral dose of 400 and 800 mg ibuprofen produced similar anti-hyperalgesic effects suggesting a ceiling effect. Tissue levels of IL-1 beta and IL-6 were not affected after the 400mg dose but decreased significantly (44+/-32% and 38+/-13%) after the 800 mg dose. These results support the utility of explored method for tracking cytokines in human tissue and suggest that anti-hyperalgesic and anti-inflammatory effects of ibuprofen are at least partially dissociated. The data further suggest that high clinical doses of ibuprofen exert anti-inflammatory effects by down-regulating tissue cytokine levels. Explored human bioassay is a promising tool for studying the pathology and pharmacology of inflammatory and chronic pain conditions.

Three-dimensional magnetic correlations in multiferroic LuFe2O4.

We present single crystal neutron diffraction measurements on multiferroic LuFe(2)O(4). Magnetic reflections are observed below transitions at 240 and 175 K indicating that the magnetic interactions in LuFe(2)O(4) are three-dimensional in character. The magnetic structure is refined as a ferrimagnetic spin configuration below the 240 K transition. Below 175 K a significant broadening of the magnetic peaks is observed along with the buildup of a diffuse component to the magnetic scattering.

Charge order superstructure with integer iron valence in Fe(2)OBO(3).

Solution-grown single crystals of Fe(2)OBO(3) were characterized by specific heat, Mössbauer spectroscopy, and x-ray diffraction. A peak in the specific heat at 340 K indicates the onset of charge order. Evidence for a doubling of the unit cell at low temperature is presented. Combining structural refinement of diffraction data and Mössbauer spectra, domains with diagonal charge order are established. Bond-valence-sum analysis indicates integer valence states of the Fe ions in the charge ordered phase, suggesting Fe(2)OBO(3) is the clearest example of ionic charge order so far.

Incommensurate charge order phase in Fe2OBO3 due to geometrical frustration.

The temperature dependence of charge order in Fe2OBO3 was investigated by resistivity and differential scanning calorimetry measurements, Mössbauer spectroscopy, and synchrotron x-ray scattering, revealing an intermediate phase between room temperature and 340 K, characterized by coexisting mobile and immobile carriers, and by incommensurate superstructure modulations with temperature-dependent propagation vector (1/2, 0, tau). The incommensurate modulations arise from specific antiphase boundaries with low energy cost due to geometrical charge frustration.

Seizure duration with remifentanil/methohexital vs. methohexital alone in middle-aged patients undergoing electroconvulsive therapy.

BACKGROUND: The object of this study was to test whether substituting part of the methohexital dose with the short-acting opioid remifentanil would prolong seizure duration in middle-aged patients while providing a similar depth of anesthesia as with methohexital alone. This has been reported for the combined use of methohexital and remifentanil in elderly patients, but has not been investigated in middle-aged patients likely to require a higher total dose of methohexital for inducing anesthesia. METHOD: Seven patients (42+/-10 years; mean +/-SD) receiving electroconvulsive therapy (ECT) were anesthetized with methohexital (1.25 mg kg-1) or with methohexital (0.625 mg kg-1) plus remifentanil (1 micro g kg-1) in this randomized, double blind, crossover study. Additional methohexital was given as needed until loss of eyelash reflex was observed. Suxamethonium (1 mg kg-1) was used for muscular paralysis. RESULTS: Motor and EEG seizure durations were significantly longer after induction with methohexital plus remifentanil (45+/-14 and 58+/-15 s) than with methohexital alone (31+/-11 and 42+/-18 s). A methohexital dose of 1.2+/-0.3 and 1.9+/-0.3 mg was necessary to achieve loss of eyelash reflex if methohexital was used with and without remifentanil. Peak heart rate after ECT was significantly higher if remifentanil was coadministered with methohexital (148+/-12 vs. 126+/-24 b.p.m). CONCLUSION: Substituting part of the methohexital dose with remifentanil is a useful anesthetic technique to prolong seizure duration in middle-aged patients requiring a 1.5-fold higher induction dose of methohexital than elderly patients, the only population studied to date for the combined use of methohexital and remifentanil in ECT.

Magneto-optical study of the superconducting gap of MgB(2) single crystals.

We present magneto-optical reflectivity results in the basal plane of the hexagonal MgB(2). The data were collected on a mosaic of MgB(2) single crystals with T(c)=38 K from the ultraviolet down to the far infrared as a function of temperature and magnetic field oriented along the c axis. In the far infrared, there is a clear signature of the superconducting gap with a gap ratio 2 Delta/k(B)T(c) approximately 1.2, well below the weak-coupling value. The gap is suppressed in an external magnetic field, which is a function of temperature. We extract the upper critical field H(c2) along the c axis. The temperature dependence of H(c2) is compatible with the Helfand-Werthamer behavior.