Acute psychiatric care: approaches to increasing the range of services and improving access and quality of care

Acute services for mental health crises are very important to service users and their supporters, and consume a substantial share of mental health resources in many countries. However, acute care is often unpopular and sometimes coercive, and the evidence on which models are best for patient experience and outcomes remains surprisingly limited, in part reflecting challenges in conducting studies with people in crisis. Evidence on best ap­proaches to initial assessment and immediate management is particularly lacking, but some innovative models involving extended assessment, brief interventions, and diversifying settings and strategies for providing support are potentially helpful. Acute wards continue to be central in the intensive treatment phase following a crisis, but new approaches need to be developed, evaluated and implemented to reducing coercion, addressing trauma, diversifying treatments and the inpatient workforce, and making decision‐making and care collaborative. Intensive home treatment services, acute day units, and community crisis services have supporting evidence in diverting some service users from hospital admission: a greater understanding of how best to implement them in a wide range of contexts and what works best for which service users would be valuable. Approaches to crisis management in the voluntary sector are more flexible and informal: such services have potential to complement and provide valuable learning for statutory sector services, especially for groups who tend to be underserved or disengaged. Such approaches often involve staff with personal experience of mental health crises, who have important potential roles in improving quality of acute care across sectors. Large gaps exist in many low‐ and middle‐income countries, fuelled by poor access to quality mental health care. Responses need to build on a foundation of existing community responses and contextually relevant evidence. The necessity of moving outside formal systems in low‐resource settings may lead to wider learning from locally embedded strategies.     

Phenyl-substituted aminomethylene-bisphosphonates inhibit human P5C reductase and show antiproliferative activity against proline-hyperproducing tumour cells

In certain cancers, such as breast, prostate and some lung and skin cancers, the gene for the enzyme catalysing the second and last step in proline synthesis, δ¹-pyrroline-5-carboxylate (P5C) reductase, has been found upregulated. This leads to a higher proline content that exacerbates the effects of the so-called proline-P5C cycle, with tumour cells effectively using this method to increase cell survival. If a method of reducing or inhibiting P5C reductase could be discovered, it would provide new means of treating cancer. To address this point, the effect of some phenyl-substituted derivatives of aminomethylene-bisphosphonic acid, previously found to interfere with the catalytic activity of plant and bacterial P5C reductases, was evaluated in vitro on the human isoform 1 (PYCR1), expressed in E. coli and affinity purified. The 3.5-dibromophenyl- and 3.5-dichlorophenyl-derivatives showed a remarkable effectiveness, with IC₅₀ values lower than 1 µM and a mechanism of competitive type against both P5C and NADPH. The actual occurrence in vivo of enzyme inhibition was assessed on myelogenous erythroleukemic K562 and epithelial breast cancer MDA-MB-231 cell lines, whose growth was progressively impaired by concentrations of the dibromo derivative ranging from 10⁻⁶ to 10⁻⁴M. Interestingly, growth inhibition was not relieved by the exogenous supply of proline, suggesting that the effect relies on the interference with the proline-P5C cycle, and not on proline starvation.     

Biogenesis of linear O-alkylfuranocoumarins: A new pathway involving 5-hydroxymarmesin

adioactivity from [³H] 5-hydroxymarmesin was incorporated into 5-methoxypsoralen by administration to leaves of Ficus carica and cut ends of Ruta graveolens. No other furanocoumarins were labelled. Trapping experiments, in which [³H]marmesin together with 5-hydroxymarmesin was administered to fig leaves and to cut ends of rue, provided good evidence that 5-hydroxymarmesin is formed by hydroxylation of marmesin. These results, together with those obtained previously with 8-hydroxymarmesin demonstrate that, in addition to the pathway which involves the hydroxylation of psoralen, the O-alkylfuranocoumarins are also formed by a pathway which involves the hydroxylation of marmesin.     

Melatonin in the seasonal response of the aphid Acyrthosiphon pisum

Aphids display life cycles largely determined by the photoperiod.During the warm long-day seasons.most aphid species reproduce by viviparous parthenogenesis.The shortening of the photoperiod in autumn induces a switch to sexual reproduction.Males and sexual females mate to produce overwintering resistant eggs.In addition to this full life cycle(holocycle),there are anholocyelic lineages that do not respond to changes in photoperiod and reproduce continuously by parthenogenesis.The molecular or hormonal events that trigger the scasonal response(i.c,induction of the sexual phenotypes)are still unknown.Although circadian synthesis of melatonin is known to play a key role in vertebrate photoperiodism,the involvement of the circadian clock and/or of the hor-mone melatonin in insect seasonal responses is not so well established.Here we show that melatonin levels in the aphid Acyrthosiphon pisum are significantly higher in holocyclice aphids reared under short days than under long days,while no differences were found between anholoeyelic aphids under the same conditions.We also found that melatonin is localized in the aphid suboesophageal ganglion(SOG)and in the thoracic ganglionic mass(TGM).In analogy to vertcbrates,insect-type arylalkxylamine N-acetyltransferases(i-AANATs)are thought to play a key role in melatonin synthesis.We measured the expression of four I-AANAT genes identified in A.pisum and localized two of them in situ in the insect central nervous systems(CNS).Levels of expression of these genes were compatible with the quantities of melatonin observed.Moreover,like melatonin,expression of these genes was found in the SOG and the TGM.     

Effects of prostaglandins E2 and F2α on lecithin biosynthesis by cultured lung cells

Transformed cells from human lung carcinoma (Line A549), resembling type II pneumocytes, were cultured in monolayer at 37°C and incubated for five hours with ³H-choline and ¹⁴C-palmitate in the presence of various concentrations of prostaglandins (PGs) E₂ and F_2α. In the control (no PG) the level of % palmitate incorporation was 13.5 × as high as that of choline, after taking isotope dilution into account. Between the concentrations studied, 0.1 and 10 μM, both prostaglandins stimulated markedly the incorporation of both precursors, though choline up to 3 × better than palmitate. This was indicated by a change in the palmitate/choline incorporation ratio from 13.5 to as low as 4.2. At the lowest PG concentration, 0.1 μM, PGE₂ was much more effective than PGF_2α in stimulating the incorporation of both precursors.     

Histochimie des colorations dans le bloc à base de métaux,application aux coupes semi-fines

Résumé Les auteurs décrivent une nouvelle méthode de coloration dans le bloc de tissu avec différents sels métalliques (alun de fer, tétroxyde d'osmium, acétate d'uranyl et chromeosmium) et l'hématoxyline. Cette technique est utilisée sur des tissus qui sont ensuite inclus en Araldit et permet d'obtenir des coupes semi-fines déjà colorées. Les auteurs ont cherché à préciser la spécificité de fixation du fer dans le tissu au moyen de méthodes d'extraction et de blocage. D'après leurs observations, le fer se fixerait aux groupes tissulaires chargés négativement. La nature des liaisons semble être de type électrostatique et complexe. Les liaisons complexes semblent prédominer au niveau des structures contenant des acides nucléiques.

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Histochemistry of block staining with metals for semifine sections

Summary The authors describe a new method of block staining for semifine sections with various metal salts (ferriammonium-sulphate, osmium tetroxyde, uranyl acetate, chromeosmium) and hematoxylin. They investigated the specificity of iron-alaun-hematoxylin with several extractions and blocking methods. According to their observations the dissociated iron is bounded to the negatively charged tissular groups. The nature of binding is thought to be electrostatic and coordinativ (complex). The last one is probably predominant in nucleic acids containing structures. This method seems to be encouraging for electron-histochemical investigations.

     

Perthamide C Inhibits eNOS and iNOS Expression and Has Immunomodulating Activity In Vivo

Here we have characterized perthamide C, a cyclopeptide from a Solomon Lithistid sponge Theonella swinhoei, which displays an anti-inflammatory/immunomodulatory activity. The study has been performed using the carragenan-induced mouse paw edema that displays an early (0–6 h) and a late phase (24–96 h). Perthamide C significantly inhibits neutrophils infiltration in tissue both in the early and late phases. This effect was coupled to a reduced expression of the endothelial nitric oxide synthase (eNOS) in the early phase while cyclooxygenase-1 and 2 (COX-1, COX-2), and inducible NOS (iNOS) expression were unaffected. In the late phase perthamide C reduced expression of both NOS isoforms without affecting COXs expression. This peculiar selectivity toward the two enzymes deputed to produce NO lead us to investigate on a possible action of perthamide C on lymphocytes infiltration and activation. We found that perthamide C inhibited the proliferation of peripheral lymphocytes, and that this effect was secondary to its metabolic activation in vivo. Indeed, in vitro perthamide C did not inhibit proliferation as opposite to its metabolite perthamide H.In conclusion, perthamide C selectively interferes with NO generation triggered by either eNOS or iNOS without affecting either COX-1 or COX-2. This in turn leads to modulation of the inflammatory response through a reduction of vascular permeability, neutrophil infiltration as well as lymphocyte proliferation.     

Genetic variation in eggplant for Nitrogen Use Efficiency under contrasting NO3‐ supply

Eggplant (Solanum melongena L.) yield is highly sensitive to N fertilization, the excessive use of which is responsible for environmental and human health damage. Lowering N input together with the selection of improved Nitrogen‐Use‐Efficiency (NUE) genotypes, more able to uptake, utilize, and remobilize N available in soils, can be challenging to maintain high crop yields in a sustainable agriculture. The aim of this study was to explore the natural variation among eggplant accessions from different origins, in response to Low (LN) and High (HN) Nitrate (NO₃^‐) supply, to identify NUE‐contrasting genotypes and their NUE‐related traits, in hydroponic and greenhouse pot experiments. Two eggplants, AM222 and AM22, were identified as N‐use efficient and inefficient, respectively, in hydroponic, and these results were confirmed in a pot experiment, when crop yield was also evaluated. Overall, our results indicated the key role of N‐utilization component (NUtE) to confer high NUE. The remobilization of N from leaves to fruits may be a strategy to enhance NUtE, suggesting glutamate synthase as a key enzyme. Further, omics technologies will be used for focusing on C‐N metabolism interacting networks. The availability of RILs from two other selected NUE‐contrasting genotypes will allow us to detect major genes/quantitative trait loci related to NUE.     

Turning regenerative technologies into treatment to repair myocardial injuries

Regenerative therapies including stem cell treatments hold promise to allow curing patients affected by severe cardiac muscle diseases. However, the clinical efficacy of stem cell therapy remains elusive, so far. The two key roadblocks that still need to be overcome are the poor cell engraftment into the injured myocardium and the limited knowledge of the ideal mixture of bioactive factors to be locally delivered for restoring heart function. Thus, therapeutic strategies for cardiac repair are directed to increase the retention and functional integration of transplanted cells in the damaged myocardium or to enhance the endogenous repair mechanisms through cell-free therapies. In this context, biomaterial-based technologies and tissue engineering approaches have the potential to dramatically impact cardiac translational medicine. This review intends to offer some consideration on the cell-based and cell-free cardiac therapies, their limitations and the possible future developments.     

An extracellular vesicle epitope profile is associated with acute myocardial infarction

The current standard biomarker for myocardial infarction (MI) is high‐sensitive troponin. Although powerful in clinical setting, search for new markers is warranted as early diagnosis of MI is associated with improved outcomes. Extracellular vesicles (EVs) attracted considerable interest as new blood biomarkers. A training cohort used for diagnostic modelling included 30 patients with STEMI, 38 with stable angina (SA) and 30 matched‐controls. Extracellular vesicle concentration was assessed by nanoparticle tracking analysis. Extracellular vesicle surface‐epitopes were measured by flow cytometry. Diagnostic models were developed using machine learning algorithms and validated on an independent cohort of 80 patients. Serum EV concentration from STEMI patients was increased as compared to controls and SA. EV levels of CD62P, CD42a, CD41b, CD31 and CD40 increased in STEMI, and to a lesser extent in SA patients. An aggregate marker including EV concentration and CD62P/CD42a levels achieved non‐inferiority to troponin, discriminating STEMI from controls (AUC = 0.969). A random forest model based on EV biomarkers discriminated the two groups with 100% accuracy. EV markers and RF model confirmed high diagnostic performance at validation. In conclusion, patients with acute MI or SA exhibit characteristic EV biomarker profiles. EV biomarkers hold great potential as early markers for the management of patients with MI.