Circadian and Ultradian Rhythms of Free Glucocorticoid Hormone Are Highly Synchronized between the Blood, the Subcutaneous Tissue, and the Brain

Total glucocorticoid hormone levels in plasma of various species, including humans, follow a circadian rhythm that is made up from an underlying series of hormone pulses. In blood most of the glucocorticoid is bound to corticosteroid-binding globulin and albumin, resulting in low levels of free hormone. Although only the free fraction is biologically active, surprisingly little is known about the rhythms of free glucocorticoid hormones. We used single-probe microdialysis to measure directly the free corticosterone levels in the blood of freely behaving rats. Free corticosterone in the blood shows a distinct circadian and ultradian rhythm with a pulse frequency of approximately one pulse per hour together with an increase in hormone levels and pulse height toward the active phase of the light/dark cycle. Similar rhythms were also evident in the subcutaneous tissue, demonstrating that free corticosterone rhythms are transferred from the blood into peripheral target tissues. Furthermore, in a dual-probe microdialysis study, we demonstrated that the circadian and ultradian rhythms of free corticosterone in the blood and the subcutaneous tissue were highly synchronized. Moreover, free corticosterone rhythms were also synchronous between the blood and the hippocampus. These data demonstrate for the first time an ultradian rhythm of free corticosterone in the blood that translates into synchronized rhythms of free glucocorticoid hormone in peripheral and central tissues. The maintenance of ultradian rhythms across tissue barriers in both the periphery and the brain has important implications for research into aberrant biological rhythms in disease and for the development of improved protocols for glucocorticoid therapy

Lattice determination of the K→(ππ)I=2K \to (\pi\pi)_{I=2} Decay Amplitude A2A_2

We describe the computation of the amplitude A_2 for a kaon to decay into two pions with isospin I=2. The results presented in the letter Phys.Rev.Lett. 108 (2012) 141601 from an analysis of 63 gluon configurations are updated to 146 configurations giving Re$A_2=1.381(46)_{\textrm{stat}}(258)_{\textrm{syst}} 10^{-8}$ GeV and Im$A_2=-6.54(46)_{\textrm{stat}}(120)_{\textrm{syst}}10^{-13}$ GeV. Re$A_2$ is in good agreement with the experimental result, whereas the value of Im$A_2$ was hitherto unknown. We are also working towards a direct computation of the $K\to(\pi\pi)_{I=0}$ amplitude $A_0$ but, within the standard model, our result for Im$A_2$ can be combined with the experimental results for Re$A_0$, Re$A_2$ and $\epsilon^\prime/\epsilon$ to give Im$A_0/$Re$A_0= -1.61(28)\times 10^{-4}$ . Our result for Im\,$A_2$ implies that the electroweak penguin (EWP) contribution to $\epsilon^\prime/\epsilon$ is Re$(\epsilon^\prime/\epsilon)_{\mathrm{EWP}} = -(6.25 \pm 0.44_{\textrm{stat}} \pm 1.19_{\textrm{syst}}) \times 10^{-4}$.Comment: 59 pages, 11 figure

Rotation and pseudo-rotation

Eigenvectors of stress-energy tensor (the source in Einstein's equations) form privileged bases in description of the corresponding space-times. When one or more of these vector fields are rotating (the property well determined in differential geometry), one says that the space-time executes this rotation. Though the rotation in its proper sense is understood as that of a timelike congruence (vector field), the rotation of a spacelike congruence is not a less objective property if it corresponds to a canonical proper basis built of the just mentioned eigenvectors. In this last case, we propose to speak on pseudo-rotation. Both properties of metric, its material sources, and space-time symmetries are considered in this paper.Comment: 13 pages, no figures, contains parts of the PhD Thesis of H. Vargas Rodr\'igue

Primary intraocular lymphoma.

Primary intraocular lymphoma (PIOL) is an ocular malignancy that is a subset of primary central system lymphoma (PCNSL). Approximately one-third of PIOL patients will have concurrent PCNSL at presentation, and 42-92% will develop PCNSL within a mean of 8-29 months. Although rare, the incidence has been rising in both immunocompromised and immunocompetent populations. The majority of PIOL is diffuse large B-cell lymphoma, though rare T-cell variants are described. Recently, PIOL has been classified by main site of involvement in the eye, with vitreoretinal lymphoma as the most common type of ocular lymphoma related to PCNSL. Diagnosis remains challenging for ophthalmologists and pathologists. PIOL can masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other neoplasms such as metastatic cancers. Laboratory diagnosis by cytology has been much aided by the use of immunocytochemistry, flow cytometry, biochemical finding of interleukin changes (IL10:IL6 ratio > 1), and cellular microdissection with polymerase chain reaction amplification for clonality. Use of several tests improves the diagnostic yield. Approaches to treatment have centered on systemic methotrexate-based chemotherapy, often with cytarabine (Ara-C) and radiotherapy. Use of intravitreal chemotherapy with methotrexate (0.4 mg/0.1 mL) is promising in controlling ocular disease, and intravitreal rituximab (anti-CD20 monoclonal antibody) has also been tried. Despite these advances, prognosis remains poor

Self-Screening Hawking Atmosphere in the Presence of a Bulk Viscosity

The recent theory of 't Hooft [ Nucl. Phys. Suppl. {\bf 68}, 174 (1998)] models the black hole as a system endowed with an envelope of matter that obeys an equation of state in the form $p=(\gamma -1)\rho$, and acts as a source in Einstein's equations. The present paper generalizes the 't Hooft theory so as to take into account a bulk viscosity $\zeta$ in the fluid. It is shown that even a slight positive value of $\zeta$ will suffice to yield complete agreement with the Hawking formula for the entropy of the black hole, if the value of the constant $\gamma$ takes a value that is slightly less than 4/3. The value $\gamma=4/3$ corresponds to a radiation fluid.Comment: 12 pages, LaTeX, no figures, minor extensions of the discussion. To appear in PR

Cortisol, Stress, and Disease—Bidirectional Associations:Role for Corticosteroid-Binding Globulin?

Selye described stress as a unified neurohormonal mechanism maintaining homeostasis. Acute stress system activation is adaptive through neurocognitive, catecholaminergic, and immunomodulation mechanisms, followed by a reset via cortisol. Stress system components, the sympathoadrenomedullary system, hypothalamic-pituitary-adrenal axis, and limbic structures are implicated in many chronic diseases by establishing an altered homeostatic state, allostasis. Consequent “primary stress system disorders” were popularly accepted, with phenotypes based on conditions such as Cushing syndrome, pheochromocytoma, and adrenal insufficiency. Cardiometabolic and major depressive disorders are candidates for hypercortisolemic etiology, contrasting the “hypocortisolemic symptom triad” of stress sensitivity, chronic fatigue, and pain. However, acceptance of chronic stress etiology requires cause-and-effect associations, and practical utility such as therapeutics altering stress system function. Inherent predispositions to stress system perturbations may be relevant. Glucocorticoid receptor (GR) variants have been associated with metabolic/neuropsychological states. The SERPINA6 gene encoding corticosteroid-binding globulin (CBG), was the sole genetic factor in a single-nucleotide variation–genome-wide association study linkage study of morning plasma cortisol, a risk factor for cardiovascular disease, with alterations in tissue-specific GR-related gene expression. Studies showed genetically predicted high cortisol concentrations are associated with hypertension and anxiety, and low CBG concentrations/binding affinity, with the hypocortisolemic triad. Acquired CBG deficiency in septic shock results in 3-fold higher mortality when hydrocortisone administration produces equivocal results, consistent with CBG's role in spatiotemporal cortisol delivery. We propose some stress system disorders result from constitutional stress system variants rather than stressors themselves. Altered CBG:cortisol buffering may influence interstitial cortisol ultradian surges leading to pathological tissue effects, an example of stress system variants contributing to stress-related disorders

The K→(ππ)I=2K\to(\pi\pi)_{I=2} Decay Amplitude from Lattice QCD

We report on the first realistic \emph{ab initio} calculation of a hadronic weak decay, that of the amplitude $A_2$ for a kaon to decay into two \pi-mesons with isospin 2. We find Re$A_2=(1.436\pm 0.063_{\textrm{stat}}\pm 0.258_{\textrm{syst}})\,10^{-8}\,\textrm{GeV}$ in good agreement with the experimental result and for the hitherto unknown imaginary part we find {Im}$\,A_2=-(6.83 \pm 0.51_{\textrm{stat}} \pm 1.30_{\textrm{syst}})\,10^{-13}\,{\rm GeV}$. Moreover combining our result for Im\,$A_2$ with experimental values of Re\,$A_2$, Re\,$A_0$ and $\epsilon^\prime/\epsilon$, we obtain the following value for the unknown ratio Im\,$A_0$/Re\,$A_0$ within the Standard Model: $\mathrm{Im}\,A_0/\mathrm{Re}\,A_0=-1.63(19)_{\mathrm{stat}}(20)_{\mathrm{syst}}\times10^{-4}$. One consequence of these results is that the contribution from Im\,$A_2$ to the direct CP violation parameter $\epsilon^{\prime}$ (the so-called Electroweak Penguin, EWP, contribution) is Re$(\epsilon^\prime/\epsilon)_{\mathrm{EWP}} = -(6.52 \pm 0.49_{\textrm{stat}} \pm 1.24_{\textrm{syst}}) \times 10^{-4}$. We explain why this calculation of $A_2$ represents a major milestone for lattice QCD and discuss the exciting prospects for a full quantitative understanding of CP-violation in kaon decays.Comment: 5 pages, 1 figur

Some distorted thoughts about ketamine as a psychedelic and a novel hypothesis based on NMDA receptor-mediated synaptic plasticity.

Ketamine, a channel blocking NMDA receptor antagonist, is used off-label for its psychedelic effects, which may arise from a combination of several inter-related actions. Firstly, reductions of the contribution of NMDA receptors to afferent information from external and internal sensory inputs may distort sensations and their processing in higher brain centres. Secondly, reductions of NMDA receptor-mediated excitation of GABAergic interneurons can result in glutamatergic overactivity. Thirdly, limbic cortical disinhibition may indirectly enhance dopaminergic and serotonergic activity. Fourthly, inhibition of NMDA receptor mediated synaptic plasticity, such as short-term potentiation (STP) and long-term potentiation (LTP), could lead to distorted memories. Here, for the first time, we compared quantitatively the effects of ketamine on STP and LTP. We report that ketamine inhibits STP in a double sigmoidal fashion with low (40 nM) and high (5.6 μM) IC50 values. In contrast, ketamine inhibits LTP in a single sigmoidal manner (IC50 value ∼ 15 μM). A GluN2D-subunit preferring NMDA receptor antagonist, UBP145, has a similar pharmacological profile. We propose that the psychedelic effects of ketamine may involve the inhibition of STP and, potentially, associated forms of working memory. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'

Feasibility of salivary cortisol collection in patients and companions attending dementia diagnostic meetings in memory clinics

OBJECTIVES: Receiving a diagnosis of dementia is life-changing for the individual and their companion. The aim of the study was to explore the feasibility of collecting salivary cortisol from patients who are informed if they have dementia and their companions. Patients and companions collected nine saliva samples in three batches: 1-2 weeks before, immediately before, and immediately after the diagnostic meeting. Each batch consisted of three samples taken in the evening, after awaking and 30 mins post-waking. RESULTS: 22.7% (N = 10) of 44 invited patients and nine companions agreed, with 18.2% patients (N = 8) and 15.9% companions (N = 7) providing samples. Participants found that saliva collection was demanding and disrupted routines. On a purely descriptive level, some indications of an increased cortisol stress response in patients diagnosed with dementia were found in this very small sample. Researchers should expect low recruitment rates in this elderly population. Simpler collection procedures, e.g. pre-labelled packages with date/time, possible omission of morning samples and objective rather than self-report assessment of waking and saliva collection times-using actigraphy wrist-watches bleeps to prompt people at the timepoints and electronic track caps-might improve adherence and improve the accuracy of timepoints when swabs were actually collected