The social underpinnings of mental distress in the time of COVID-19 – time for urgent action

We argue that predictions of a ‘tsunami’ of mental health problems as a consequence of the pandemic of coronavirus disease 2019 (COVID-19) and the lockdown are overstated; feelings of anxiety and sadness are entirely normal reactions to difficult circumstances, not symptoms of poor mental health. Some people will need specialised mental health support, especially those already leading tough lives; we need immediate reversal of years of underfunding of community mental health services. However, the disproportionate effects of COVID-19 on the most disadvantaged, especially BAME people placed at risk by their social and economic conditions, were entirely predictable. Mental health is best ensured by urgently rebuilding the social and economic supports stripped away over the last decade. Governments must pump funds into local authorities to rebuild community services, peer support, mutual aid and local community and voluntary sector organisations. Health care organisations must tackle racism and discrimination to ensure genuine equal access to universal health care. Government must replace highly conditional benefit systems by something like a universal basic income. All economic and social policies must be subjected to a legally binding mental health audit. This may sound unfeasibly expensive, but the social and economic costs, not to mention the costs in personal and community suffering, though often invisible, are far greater

Potency enhancement of the κ-opioid receptor antagonist probe ML140 through sulfonamide constraint utilizing a tetrahydroisoquinoline motif

Optimization of the sulfonamide-based kappa opioid receptor (KOR) antagonist probe molecule ML140 through constraint of the sulfonamide nitrogen within a tetrahydroisoquinoline moiety afforded a marked increase in potency. This strategy, when combined with additional structure-activity relationship exploration, has led to a compound only six-fold less potent than norBNI, a widely utilized KOR antagonist tool compound, but significantly more synthetically accessible. The new optimized probe is suitably potent for use as an in vivo tool to investigate the therapeutic potential of KOR antagonists

Development of functionally selective, small molecule agonists at kappa opioid receptors

The kappa opioid receptor (KOR) is widely expressed in the CNS and can serve as a means to modulate pain perception, stress responses, and affective reward states. Therefore, the KOR has become a prominent drug discovery target toward treating pain, depression, and drug addiction. Agonists at KOR can promote G protein coupling and βarrestin2 recruitment as well as multiple downstream signaling pathways, including ERK1/2 MAPK activation. It has been suggested that the physiological effects ofKORactivation result from different signaling cascades, with analgesia being G protein-mediated and dysphoria being mediated through βarrestin2 recruitment. Dysphoria associated with KOR activation limits the therapeutic potential in the use of KOR agonists as analgesics; therefore, it may be beneficial to develop KOR agonists that are biased toward G protein coupling and away from βarrestin2 recruitment. Here, we describe two classes of biased KOR agonists that potently activateGprotein coupling but weakly recruitβarrestin2. These potent and functionally selective small molecule compounds may prove to be useful tools for refining the therapeutic potential of KOR-directed signaling in vivo

Retardadores de crescimento no desenvolvimento e na qualidade ornamental de Zinnia elegans Jacq. 'Lilliput' envasada

As zínias têm grande potencial como plantas floríferas envasadas e representam rápida fonte de novidade para a floricultura com o auxílio de retardadores de crescimento. Avaliaram-se os efeitos de retardadores de crescimento no desenvolvimento e na produção de plantas envasadas de porte baixo, compactas e atrativas de 'Lilliput' Zinnia elegans, cultivar altamente ornamental, com sementes de baixo custo. O delineamento experimental foi em blocos casualizados, com dez tratamentos (controle e três concentrações de cada retardador: daminozide, paclobutrazol e chlormequat) e quatro repetições (dois vasos por unidade experimental, com uma planta por vaso de 0,6 L). Paclobutrazol (0,5; 0,75 e 1,0 mg i.a. por vaso) e chlormequat (1,0; 2,0 e 3,0 g L-1) foram aplicados ao substrato (40 mL por vaso), enquanto o daminozide (2,5; 3,75 e 5,0 g L-1) foi aplicado através de pulverização foliar (10 mL por vaso), no estádio de gema floral apical visível. Daminozide (2,5 e 3,75 g L-1), paclobutrazol (0,5; 0,75 e 1,0 mg i.a. por vaso) e 1,0 g L-1 de chlormequat reduziram significativamente a altura das plantas e o comprimento dos ramos laterais, sem afetar o diâmetro dos capítulos, atrasar o ciclo de produção e causar fitotoxicidade. Entretanto, as plantas não se apresentaram suficientemente baixas e compactas para atender às exigências de qualidade do mercado. Chlormequat (2,0 e 3,0 g L-1) causou fitotoxicidade e daminozide (5,0 g L-1) aumentou o ciclo de produção.Zinnias have good potential to be used as flowering, potted plants, being a quick source of novelty for the floriculture industry with the aid of growth retardants. This study evaluated the effect of growth retardants on development and production of short, compact and attractive plants of potted 'Lilliput' Zinnia elegans, a highly ornamental zinnia with low cost seeds. Trials were set up in randomized blocks, with ten treatments (control and three treatments of each retardant: daminozide, paclobutrazol and chlormequat) and four replications (two pots per experimental unit, with one plant per 0.6-L pot). Paclobutrazol (0.5, 0.75 and 1.0 mg a.i. per pot) and chlormequat (1.0, 2.0 and 3.0 g L-1) were applied as a single drench (40 mL per pot), and daminozide (2.5, 3.75 and 5.0 g L-1) as a single foliar spray to runoff (10 mL per pot), at apical flower bud stage. Daminozide (2.5 and 3.75 g L-1), paclobutrazol (0.5, 0.75 and 1.0 mg a.i. per pot) and chlormequat at 1.0 g L-1 significantly reduced plant height and side branches length, without affecting flower diameter, delaying production cycle and causing phytotoxicity symptoms. However, plants were not short and compact enough to meet market quality demand. Chlormequat (2.0 and 3.0 g L-1) caused phytotoxicity symptoms and daminozide (5.0 g L-1) delayed production cycle

Feeding strategies and energy to protein ratio on tambaqui performance and physiology

The objective of this work was to evaluate the effect of feed deprivation and refeeding with diets containing different energy to protein ratios (E/P) on the performance and physiology of juvenile tambaqui (Colossoma macropomum). A 4x2 factorial arrangement with three replicates was used, with four E/P ratios (11.5, 10.5, 9.5, and 8.5 kcal g-1 digestible energy per protein) and two feeding regimens (with and without deprivation), during 60 days. Fish from the food-deprived group were fasted for 14 days and refed from the fifteenth to the sixtieth day, whereas the remaining fish were fed for 60 days. At the end of the experimental period, weight of fish subjected to food deprivation was lower than that of those continuously fed; however, this condition did not influence the physiological parameters analyzed. Tambaqui fed 11.5 kcal g-1 achieved lower final weight than those fed with the other diets, in both regimens. Among the physiological parameters, only plasma protein presented significant increase in fish fed 8.5 kcal g-1, in both feeding regimens, probably due to the higher dietary protein concentration. These results indicate that fish show a partial compensatory growth, and that 10.5 kcal g-1 can be recommended for the diet of juvenile tambaqui

Search for the doubly heavy baryon Ξbc+\it{\Xi}_{bc}^{+} decaying to J/ψΞc+J/\it{\psi} \it{\Xi}_{c}^{+}

A first search for the $\it{\Xi}_{bc}^{+}\to J/\it{\psi}\it{\Xi}_{c}^{+}$ decay is performed by the LHCb experiment with a data sample of proton-proton collisions, corresponding to an integrated luminosity of $9\,\mathrm{fb}^{-1}$ recorded at centre-of-mass energies of 7, 8, and $13\mathrm{\,Te\kern -0.1em V}$. Two peaking structures are seen with a local (global) significance of $4.3\,(2.8)$ and $4.1\,(2.4)$ standard deviations at masses of $6571\,\mathrm{Me\kern -0.1em V\!/}c^2$ and $6694\,\mathrm{Me\kern -0.1em V\!/}c^2$, respectively. Upper limits are set on the $\it{\Xi}_{bc}^{+}$ baryon production cross-section times the branching fraction relative to that of the $B_{c}^{+}\to J/\it{\psi} D_{s}^{+}$ decay at centre-of-mass energies of 8 and $13\mathrm{\,Te\kern -0.1em V}$, in the $\it{\Xi}_{bc}^{+}$ and in the $B_{c}^{+}$ rapidity and transverse-momentum ranges from 2.0 to 4.5 and 0 to $20\,\mathrm{Ge\kern -0.1em V\!/}c$, respectively. Upper limits are presented as a function of the $\it{\Xi}_{bc}^{+}$ mass and lifetime.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-005.html (LHCb public pages

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe