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Animal survival in fluctuating environments depend on the ability to modulate their developmental pace in response to nutrient availability, a phenomenon known as developmental plasticity. In Drosophila larvae, we uncover a critical endocrine mechanism that coordinates this process under conditions of amino acid restriction. We identify the peptide hormone Limostatin as an enterokine, produced by a small population of midgut enteroendocrine cells, that acts systemically to inhibit the expression and release of dILP2, the major insulin-like peptide controlling developmental progression. Limostatin expression in enteroendocrine cells is triggered by reduced amino acid availability through an inter-organ relay involving the fat body and neuroendocrine insulin-producing cells in the brain. Limostatin participates in a feedback control loop that slows down developmental progression once systemic nutrient shortage is sensed. This gut-brain axis enables larvae to preserve viability under nutritional stress. Our findings define the larval gut as a nutrient-sensitive endocrine organ and position Limostatin as a key regulator of developmental plasticity. Our work expands the concept of decretins to include developmental pace control, suggesting that enterokines that regulate IGF signalling, rather than insulin release per se, may represent an evolutionarily conserved or convergent strategy in regulating developmental plasticity.

To determine the efficacy of fluoride varnish (5% NaF, Duraphat®, Colgate) added to caregiver counseling to prevent early childhood caries, we conducted a two-year randomized, dental-examiner-masked clinical trial. Initially, 376 caries-free children, from low-income Chinese or Hispanic San Francisco families, were enrolled (mean age ± standard deviation, 1.8 ± 0.6 yrs). All families received counseling, and children were randomized to the following groups: no fluoride varnish, fluoride varnish once/year, or fluoride varnish twice/year. An unexpected protocol deviation resulted in some children receiving less active fluoride varnish than assigned. Intent-to-treat analyses showed a fluoride varnish protective effect in caries incidence, p < 0.01. Analyzing the number of actual, active fluoride varnish applications received resulted in a dose-response effect, p < 0.01. Caries incidence was higher for ‘counseling only’ vs. ‘counseling + fluoride varnish assigned once/year’ (OR = 2.20, 95% CI 1.19–4.08) and ‘twice/year’ (OR = 3.77, 95% CI 1.88–7.58). No related adverse events were reported. Fluoride varnish added to caregiver counseling is efficacious in reducing early childhood caries incidence.

Cyanobacteria are a well-known source of bioproducts which renders culturable strains a valuable resource for biotechnology purposes. We describe here the establishment of a cyanobacterial culture collection (CC) and present the first version of the strain catalog and its online database (http://lege.ciimar.up.pt/). The LEGE CC holds 386 strains, mainly collected in coastal (48%), estuarine (11%), and fresh (34%) water bodies, for the most part from Portugal (84%). By following the most recent taxonomic classification, LEGE CC strains were classified into at least 46 genera from six orders (41% belong to the Synechococcales), several of them are unique among the phylogenetic diversity of the cyanobacteria. For all strains, primary data were obtained and secondary data were surveyed and reviewed, which can be reached through the strain sheets either in the catalog or in the online database. An overview on the notable biodiversity of LEGE CC strains is showcased, including a searchable phylogenetic tree and images for all strains. With this work, 80% of the LEGE CC strains have now their 16S rRNA gene sequences deposited in GenBank. Also, based in primary data, it is demonstrated that several LEGE CC strains are a promising source of extracellular polymeric substances (EPS). Through a review of previously published data, it is exposed that LEGE CC strains have the potential or actual capacity to produce a variety of biotechnologically interesting compounds, including common cyanotoxins or unprecedented bioactive molecules. Phylogenetic diversity of LEGE CC strains does not entirely reflect chemodiversity. Further bioprospecting should, therefore, account for strain specificity of the valuable cyanobacterial holdings of LEGE CC.

We have previously shown that Environmental Enrichment (EE)-consisting of social support, novelty, and open spaces-decreased disease progression and anxiety in a rat model of endometriosis. We developed a novel EE intervention to be tested in a pilot randomized clinical trial (RCT) in patients with endometriosis, a painful, stressful disease. To translate and evaluate the feasibility and acceptability of an adapted EE intervention as an adjuvant to standard-of-care for endometriosis patients. Feasibility was assessed through recruitment, enrollment, and adherence rates. Acceptability was evaluated through a post-intervention survey and focus group discussion 3-months after the end of the intervention. Of the 103 subjects recruited, 64 were randomized to the intervention group and 39 to the control group. At the start of the intervention, the study groups consisted of 29 (intervention) and 27 (control) subjects. Enrollment rates were 45.3% and 69.2%, and adherence rates were 41.4% and 100% for the intervention and control groups, respectively. Delays resulting from natural events (earthquakes, the COVID-19 pandemic) impacted enrollment and adherence rates. The most common reasons for missing an intervention were period pain (39.1%) and work-study (34.8%). There was high acceptability (>80%) of the intervention's logistics. The majority (82.4%) of subjects would continue participating in support groups regularly, and 95.7% would recommend the intervention to other patients. We showed that EE could be translated into an acceptable integrative multi-modal therapy perceived as valuable among participants who completed the intervention. High attrition/low adherence indicates that additional refinements would be needed to improve feasibility. Acceptability data indicate that EE has the potential to be integrated into the clinical management of patients with endometriosis and other inflammatory, painful disorders. Studies are ongoing to assess the efficacy of EE in improving pain symptoms, mental health, and quality of life (QoL).

Hyaluronic acid (HA) intraarticular injection is used in the management of osteoarthritis in veterinary medicine. However, HA oral administration is less common given the scarce currently available scientific evidence. This study was aimed at evaluating the effects of oral HA administration on synovial fluid concentrations of several selected biomarkers in dogs with cranial cruciate ligament (CCL) injury operated on using the tibial tuberosity advancement (TTA) technique. Fifty-five dogs were included in this prospective, randomized, double-blind, clinical study; they were randomly assigned to receive either a placebo (group A; n = 25) or HA (group B; n = 30) orally for 10 weeks. Synovial fluid samples were obtained before surgery, and at 10 weeks postoperatively to measure concentrations of HA, haptoglobin, nitric oxide, and paraoxonase-1. After 10 weeks, group HA showed a significant increase in HA concentration (p = 0.0016) and a significant decrease in PON-1 concentration (p = 0.011) compared to baseline. In conclusion, post-op oral HA administration in canine patients with CCL injury leads to improvements in osteoarthritis biomarkers, namely higher synovial fluid HA concentrations and reduced synovial fluid paraoxonase-1 concentrations. These findings support the bioavailability of orally-administered HA and its usefulness in improving biomarkers of osteoarthritis.

Objectives The goal of the current study was to investigate the universality of the five-factor model of mindfulness and the measurement equivalence of the Five-Facet Mindfulness Questionnaire (FFMQ). Methods The study used FFMQ data from published and unpublished research conducted in 16 countries (total N  = 8541). Using CFA, different models, proposed in the literature, were fitted. To test the cross-cultural equivalence of the best fitting model, a multi-group confirmatory factor analysis was used. Further, the equivalence of individual facets of the FFMQ and potential sources of non-equivalence was explored. Results The best fitting models in most samples were a five-facet model with a higher-order mindfulness factor and uncorrelated positive and negative item-wording factors and a five-facet model with a correlated facets and uncorrelated positive and negative item-wording factors. These models showed structural equivalence, but did not show metric equivalence (equivalent factor loadings) across cultures. Given this lack of equivalent factor loadings, not even correlations or mean patterns can be compared across cultures. A similar pattern was observed when testing the equivalence of the individual facets; all individual facets failed even tests of metric equivalence. A sample size weighted exploratory factor analysis across cultures indicated that a six-factor solution might provide the best fit across cultures with acting with awareness split into two factors. Finally, both the five- and six-factor solution showed substantially better fit in more individualistic and less tight cultures. Conclusions Overall, the FFMQ has conceptual and measurement problems in a cross-cultural context, raising questions about the validity of the current conceptualization of mindfulness across cultures. The results showed that the fit of the FFMQ was substantially better in individualistic cultures that indicate that further data from non-Western cultures is needed to develop a universal conceptualization and measurement of mindfulness.

BackgroundIdentification of patients on admission to hospital with coronavirus infectious disease 2019 (COVID-19) pneumonia who can develop poor outcomes has not yet been comprehensively assessed.ObjectiveTo compare severity scores used for community-acquired pneumonia to identify high-risk patients with COVID-19 pneumonia.DesignPSI, CURB-65, qSOFA, and MuLBSTA, a new score for viral pneumonia, were calculated on admission to hospital to identify high-risk patients for in-hospital mortality, admission to an intensive care unit (ICU), or use of mechanical ventilation. Area under receiver operating characteristics curve (AUROC), sensitivity, and specificity for each score were determined and AUROC was compared among them.ParticipantsPatients with COVID-19 pneumonia included in the SEMI-COVID-19 Network.Key resultsWe examined 10,238 patients with COVID-19. Mean age of patients was 66.6 years and 57.9% were males. The most common comorbidities were as follows: hypertension (49.2%), diabetes (18.8%), and chronic obstructive pulmonary disease (12.8%). Acute respiratory distress syndrome (34.7%) and acute kidney injury (13.9%) were the most common complications. In-hospital mortality was 20.9%. PSI and CURB-65 showed the highest AUROC (0.835 and 0.825, respectively). qSOFA and MuLBSTA had a lower AUROC (0.728 and 0.715, respectively). qSOFA was the most specific score (specificity 95.7%) albeit its sensitivity was only 26.2%. PSI had the highest sensitivity (84.1%) and a specificity of 72.2%.ConclusionsPSI and CURB-65, specific severity scores for pneumonia, were better than qSOFA and MuLBSTA at predicting mortality in patients with COVID-19 pneumonia. Additionally, qSOFA, the simplest score to perform, was the most specific albeit the least sensitive.

This study aimed to identify pruning intensity and frequency that can be applied to eucalypt without imposing growth reduction, in an agroforestry system in Brazil (17°36’ S and 46°42’ W). Pruning treatments included removal of 0, 1/4 and 1/3 of the live crown height (LCH) with or without the removal of some thick branches above this height (TBA), in three or four lifts, which started at 9 months. There was no effect of pruning on tree height. Diameter (dbh) and volume per tree decreased (P ≤ 0.05) only with the removal of 1/3 of the LCH + TBA, of all trees of the stand, in three lifts, up to 36 months. The Weibull diameter distribution curves showed a higher proportion of trees in the greatest diameter classes with the removal of 1/4 or 1/3 of the LCH + TBA of selected trees, in four lifts, at the age of 36 months. The time required for applying pruning to a height of 6 m did not differ among treatments (P > 0.05). Pruning up to 1/3 of the LCH + TBA of selected trees, in 4 lifts (6-month intervals) is recommended because there was a higher proportion of trees in the greatest diameter classes and the dbh at the time of the last pruning was smaller than for the other treatments, which implies in reduced knotty core. The production of trees with larger diameter and reduced knotty core may increase farmers’ income and reduce the pressure on native forests.

A case study highlighting HIV-1-associated nephropathy is presented. Antiretroviral treatment can improve glomerular and tubular histopathological changes of HIV-1-associated nephropathy in dialysis-dependent patients.

The objective of the present study was to evaluate the role of P-selectin in patients with cancer with suspected thromboembolic events (TEEs). Patients with cancer have a four times greater risk of developing TEEs. P-selectin is a glycoprotein that has the function of facilitating the interaction (adhesion) of leukocytes with the endothelium, or with platelets. There is a well-defined relationship between P-selectin and thrombosis; however, it is likely that the cut-off value of P-selectin for patients with cancer should be considered differently from that of the general population. In the present report, a prospective cross-sectional study was performed with patients of the Cancer Hospital of Barretos who were suspected of having TEEs. Among the 178 study participants, 167 (93.82%) were suspected of having deep vein thrombosis, while 59 of them (35.33%) were confirmed as such; and 11 (6.18%) were suspected of having pulmonary thromboembolism, while 3 of them were confirmed as such (27.69%). The mean results obtained were: P-selectin, 25.37 ng/ml; and D-dimer, 2,181.22 ng/ml. The P-selectin levels averaged 33.60 ng/ml with the confirmed TEE group compared with 20.40 ng/ml with the unconfirmed TEE group, with a standard deviation of 23.35 compared with 6.92 (P<0.001); and the level of D-dimer was 4,615.38 ng/ml compared with 977.52 ng/ml, with a standard deviation of 6,460.54 compared with 2,145.50 (P<0.001). Multiple logistic regression adjusted for distant metastases and the Eastern Cooperative Oncology Group (ECOG) score (2,3 and 4) were constructed. The cut-off value of P-selectin for patients with cancer was identified to be different from that reported in the literature for the general population, and the models using D-dimer and P-selectin therefore have been demonstrated to be a potentially useful tool to be used in a panel of tests to predict TEEs, either independently or in a prediction score.