The influence of μ-opioid and noradrenaline reuptake inhibition in the modulation of pain responsive neurones in the central amygdala by tapentadol in rats with neuropathy

Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurones of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbine reversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and α2-adrenoceptors seen at spinal levels, but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain

Reversible spin-optical interface in luminescent organic radicals

Molecules present a versatile platform for quantum information science, and are candidates for sensing and computation applications. Robust spin-optical interfaces are key to harnessing the quantum resources of materials. To date, carbon-based candidates have been non-luminescent, which prevents optical read-out. Here we report the first organic molecules displaying both efficient luminescence and near-unity generation yield of high-spin multiplicity excited states. This is achieved by designing an energy resonance between emissive doublet and triplet levels, here on covalently coupled tris(2,4,6-trichlorophenyl) methyl-carbazole radicals (TTM-1Cz) and anthracene. We observe the doublet photoexcitation delocalise onto the linked acene within a few picoseconds and subsequently evolve to a pure high spin state (quartet for monoradicals, quintet for biradical) of mixed radical-triplet character near 1.8 eV. These high-spin states are coherently addressable with microwaves even at 295 K, with optical read-out enabled by intersystem crossing to emissive states. Furthermore, for the biradical, on return to the ground state the previously uncorrelated radical spins either side of the anthracene show strong spin correlation. Our approach simultaneously supports a high efficiency of initialisation, spin manipulations and light-based read-out at room temperature. The integration of luminescence and high-spin states creates an organic materials platform for emerging quantum technologies

Palatal development of preterm and low birthweight infants compared to term infants – What do we know? Part 1: The palate of the term newborn

BACKGROUND: The evidence on prematurity as 'a priori' a risk for palatal disturbances that increase the need for orthodontic or orthognathic treatment is still weak. Further well-designed clinical studies are needed. The objective of this review is to provide a fundamental analysis of methodologies, confounding factors, and outcomes of studies on palatal development. One focus of this review is the analysis of studies on the palate of the term newborn, since knowing what is 'normal' is a precondition of being able to assess abnormalities. METHODS: A search profile based on Cochrane search strategies applied to 10 medical databases was used to identify existing studies. Articles, mainly those published before 1960, were identified from hand searches in textbooks, encyclopedias, reference lists and bibliographies. Sources in English, German, and French of more than a century were included. Data for term infants were recalculated if particular information about weight, length, or maturity was given. The extracted values, especially those from non-English paper sources, were provided unfiltered for comparison. RESULTS: The search strategy yielded 182 articles, of which 155 articles remained for final analysis. Morphology of the term newborn's palate was of great interest in the first half of the last century. Two general methodologies were used to assess palatal morphology: visual and metrical descriptions. Most of the studies on term infants suffer from lack of reliability tests. The groove system was recognized as the distinctive feature of the infant palate. The shape of the palate of the term infant may vary considerably, both visually and metrically. Gender, race, mode of delivery, and nasal deformities were identified as causes contributing to altered palatal morphology. Until today, anatomical features of the newborn's palate are subject to a non-uniform nomenclature. CONCLUSION: Today's knowledge of a newborn's 'normal' palatal morphology is based on non-standardized and limited methodologies for measuring a three-dimensional shape. This shortcoming increases bias and is the reason for contradictory research results, especially if pathologic conditions like syndromes or prematurity are involved. Adequate measurement techniques are needed and the 'normal palatal morphology' should be defined prior to new clinical studies on palatal development

Long-term decline of the Amazon carbon sink

Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades1, 2, with a substantial fraction of this sink probably located in the tropics3, particularly in the Amazon4. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity5. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale1, 2, and is contrary to expectations based on models6

Diagnostic prediction model development using data from dried blood spot proteomics and a digital mental health assessment to identify major depressive disorder among individuals presenting with low mood.

With less than half of patients with major depressive disorder (MDD) correctly diagnosed within the primary care setting, there is a clinical need to develop an objective and readily accessible test to enable earlier and more accurate diagnosis. The aim of this study was to develop diagnostic prediction models to identify MDD patients among individuals presenting with subclinical low mood, based on data from dried blood spot (DBS) proteomics (194 peptides representing 115 proteins) and a novel digital mental health assessment (102 sociodemographic, clinical and personality characteristics). To this end, we investigated 130 low mood controls, 53 currently depressed individuals with an existing MDD diagnosis (established current MDD), 40 currently depressed individuals with a new MDD diagnosis (new current MDD), and 72 currently not depressed individuals with an existing MDD diagnosis (established non-current MDD). A repeated nested cross-validation approach was used to evaluate variation in model selection and ensure model reproducibility. Prediction models that were trained to differentiate between established current MDD patients and low mood controls (AUC = 0.94 ± 0.01) demonstrated a good predictive performance when extrapolated to differentiate between new current MDD patients and low mood controls (AUC = 0.80 ± 0.01), as well as between established non-current MDD patients and low mood controls (AUC = 0.79 ± 0.01). Importantly, we identified DBS proteins A1AG1, A2GL, AL1A1, APOE and CFAH as important predictors of MDD, indicative of immune system dysregulation; as well as poor self-rated mental health, BMI, reduced daily experiences of positive emotions, and tender-mindedness. Despite the need for further validation, our preliminary findings demonstrate the potential of such prediction models to be used as a diagnostic aid for detecting MDD in clinical practice

Research data supporting 'Reversible spin-optical interface in luminescent organic radicals'

Contains data from optical spectroscopy, electron spin resonance, optically detected magnetic resonance, and theoretical calculations.Royal Society - URF\R1\201300 [Evans] Leverhulme Trust - ECF-2019-054 [Evans] RCUK | Engineering and Physical Sciences Research Council (EPSRC) - EP/W018519/1 [Evans] EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) - 101020167 [Gorgon] RCUK | Engineering and Physical Sciences Research Council (EPSRC) - EP/S022953/1 [Gorgon] National Natural Science Foundation of China (National Science Foundation of China) - 51925303 [Lv] Deutsche Forschungsgemeinschaft (German Research Foundation) - GRK2112 [Gruene] Bavarian Ministry of the Environment and Consumer Protection ("Solar Technologies Go Hybrid"); [Gruene] RCUK | Engineering and Physical Sciences Research Council (EPSRC) - EP/S022953/1 [Drummond] Oxford University | John Fell Fund, University of Oxford (John Fell OUP Research Fund) - 0007019 [Myers] RCUK | Engineering and Physical Sciences Research Council (EPSRC) - EP/V036408/1 [Myers] RCUK | Engineering and Physical Sciences Research Council (EPSRC) - EP/L011972/1 [Myers] Department of Chemistry, University of Oxford; [Myers] Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research) - 2.5020.11 [Londi] Walloon Region, grant no. 1117545; [Londi] Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research) - 2.5020.11 [Ricci] Walloon Region, grant no. 1117545;, Fonds pour la formation à la Recherche dans l’Industrie et dans l’Agriculture of the F.R.S.-F.N.R.S.; [Ricci] Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research) - 2.5020.11 [Valverde] Walloon Region, grant no. 1117545; [Valverde] Eusko Jaurlaritza (Basque Government) - 2019-CIEN-000092-01 [Tonnelé] Eusko Jaurlaritza (Basque Government) - PIBA19-0004 [Tonnelé] Ministerio de Ciencia e Innovación (MICINN) of Spain, project PID2019-109555GB-I00;, Donostia International Physics Centre;, Gipuzkoa’s council joint program Women and Science;, DIPC Computer Centre [Tonnelé] Eusko Jaurlaritza (Basque Government) - 2019-CIEN-000092-01 [Casanova] Eusko Jaurlaritza (Basque Government) - PIBA19-0004 [Casanova] Ministerio de Ciencia e Innovación (MICINN) of Spain, project PID2019-109555GB-I00;, DIPC Computer Centre [Casanova] Deutsche Forschungsgemeinschaft (German Research Foundation) - GRK2112 [Sperlich] Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research) - 2.5020.11 [Beljonne] Walloon Region, grant no. 1117545;, Consortium des Équipements de Calcul Intensif (CÉCI);, Tier-1 supercomputer of the Fedération Wallonie-Bruxelles [Beljonne] Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research) - 2.5020.11 [Olivier] Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research) - F.4534.21 (MIS-IMAGINE) [Olivier] Walloon Region, grant no. 1117545; [Olivier] National Natural Science Foundation of China (National Science Foundation of China) - 51925303 [Li] EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) - 101020167 [Friend] Simons Foundation - 601946 [Friend] Bavarian Ministry of the Environment and Consumer Protection ("Solar Technologies Go Hybrid"); [Dyakonov

Reversible spin-optical interface in luminescent organic radicals.

Molecules present a versatile platform for quantum information science1,2 and are candidates for sensing and computation applications3,4. Robust spin-optical interfaces are key to harnessing the quantum resources of materials5. To date, carbon-based candidates have been non-luminescent6,7, which prevents optical readout via emission. Here we report organic molecules showing both efficient luminescence and near-unity generation yield of excited states with spin multiplicity S > 1. This was achieved by designing an energy resonance between emissive doublet and triplet levels, here on covalently coupled tris(2,4,6-trichlorophenyl) methyl-carbazole radicals and anthracene. We observed that the doublet photoexcitation delocalized onto the linked acene within a few picoseconds and subsequently evolved to a pure high-spin state (quartet for monoradical, quintet for biradical) of mixed radical-triplet character near 1.8 eV. These high-spin states are coherently addressable with microwaves even at 295 K, with optical readout enabled by reverse intersystem crossing to emissive states. Furthermore, for the biradical, on return to the ground state the previously uncorrelated radical spins either side of the anthracene shows strong spin correlation. Our approach simultaneously supports a high efficiency of initialization, spin manipulations and light-based readout at room temperature. The integration of luminescence and high-spin states creates an organic materials platform for emerging quantum technologies