Oxidative stress induction by essential oil from Piper alatipetiolatum (Piperaceae) triggers lethality in the larvae of Culex quinquefasciatus (Diptera: Culicidae).

Culex quinquefasciatus is the main vector of lymphatic filariasis in Brazil, which present resistance to commercial insecticides. Nowadays, essential oils (EOs) exhibiting larvicidal activity, such as those derived from Piper alatipetiolatum, provide a promising alternative for vector control, including Culex species. This study aimed to investigate the larvicidal activity and the oxidative stress indicators of the EO from P. alatipetiolatum in Cx. quinquefasciatus larvae. The EO was extracted from P. alatipetiolatum leaves using the hydrodistillation method, resulting in a yield of 7.2 ± 0.1%, analysed by gas chromatography coupled with spectrometry and gas chromatography coupled with flame ionization detector (GC-MS and GC-FID), and evaluated against Cx. quinquefasciatus larvae. Reactive Oxygen and Nitrogen Species (RONS), Catalase (CAT), glutathione-S-transferase (GST), acetylcholinesterase (AChE), and Thiol levels were used as oxidative stress indicators. Analysis by CG-MS and CG-FID revealed that the main compound in the EO was the oxygenated sesquiterpene ishwarone, constituting 78.6% of the composition. Furthermore, the EO exhibited larvicidal activity, ranging from 26 to 100%, with an LC50 of 4.53 µg/mL and LC90 of 15.37 µg/mL. This activity was accompanied by a significant increase in RONS production, alterations in CAT, GST, AChE activity, and thiol levels compared to the control groups (p < 0.05). To the best of our knowledge, this is the first report describing the larvicidal activity and oxidative stress induced by the EO from P. alatipetiolatum against Cx. quinquefasciatus larvae. Therefore, we propose that this EO shows promise as larvicidal agent for the effective control of Cx. quinquefasciatus larvae.

Tracers and Imaging of Fatty Acid and Energy Metabolism of Human Adipose Tissues.

White adipose tissue and brown adipose tissue (WAT and BAT) regulate fatty acid metabolism and control lipid fluxes to other organs. Dysfunction of these key metabolic processes contributes to organ insulin resistance and inflammation leading to chronic diseases such as type 2 diabetes, metabolic dysfunction-associated steatohepatitis, and cardiovascular diseases. Metabolic tracers combined with molecular imaging methods are powerful tools for the investigation of these pathogenic mechanisms. Herein, I review some of the positron emission tomography and magnetic resonance imaging methods combined with stable isotopic metabolic tracers to investigate fatty acid and energy metabolism, focusing on human WAT and BAT metabolism. I will discuss the complementary strengths offered by these methods for human investigations and current gaps in the field.

Brazilian Psychiatric Association guidelines on the integration of spirituality into mental health clinical practice: Part 1. Spiritual history and differential diagnosis

Objectives: To present evidence-based guidelines for clinical practice regarding religiosity and spirituality in mental health care in Brazil. Methods: A systematic review was conducted to identify potentially eligible articles indexed in the PubMed, PsycINFO, SciELO, LILACS, and Cochrane databases. A summary of recommendations and their levels of evidence was produced in accordance with Oxford Centre for Evidence-Based Medicine guidelines. Results: The systematic review identified 6,609 articles, 41 of which satisfied all inclusion criteria. Taking a spiritual history was found to be an essential part of a compassionate and culturally sensitive approach to care. It represents a way of obtaining relevant information about the patient's religiosity/spirituality, potential conflicts that could impact treatment adherence, and improve patient satisfaction. Consistent evidence shows that reported perceptual experiences are unreliable for differentiating between anomalous experiences and psychopathology. Negative symptoms, cognitive and behavioral disorganization, and functional impairment are more helpful for distinguishing pathological and non-pathological anomalous experiences. Conclusion: Considering the importance of religiosity/spirituality for many patients, a spiritual history should be routinely included in mental health care. Anomalous experiences are highly prevalent, requiring a sensitive and evidence-based approach to differential diagnosis.

Brazilian Psychiatric Association guidelines on the integration of spirituality into mental health clinical practice: Part 1. Spiritual history and differential diagnosis.

OBJECTIVES: To present evidence-based guidelines for clinical practice regarding religiosity and spirituality in mental health care in Brazil. METHODS: A systematic review was conducted to identify potentially eligible articles indexed in the PubMed, PsycINFO, SciELO, LILACS, and Cochrane databases. A summary of recommendations and their levels of evidence was produced in accordance with Oxford Centre for Evidence-Based Medicine guidelines. RESULTS: The systematic review identified 6,609 articles, 41 of which satisfied all inclusion criteria. Taking a spiritual history was found to be an essential part of a compassionate and culturally sensitive approach to care. It represents a way of obtaining relevant information about the patient's religiosity/spirituality, potential conflicts that could impact treatment adherence, and improve patient satisfaction. Consistent evidence shows that reported perceptual experiences are unreliable for differentiating between anomalous experiences and psychopathology. Negative symptoms, cognitive and behavioral disorganization, and functional impairment are more helpful for distinguishing pathological and non-pathological anomalous experiences. CONCLUSION: Considering the importance of religiosity/spirituality for many patients, a spiritual history should be routinely included in mental health care. Anomalous experiences are highly prevalent, requiring a sensitive and evidence-based approach to differential diagnosis.

Comparative Efficacy of Venetoclax-Based Combination Therapies and Other Therapies in Treatment-Naive Patients With Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy: A Network Meta-Analysis.

OBJECTIVES: This network meta-analysis (NMA) assessed the efficacy of venetoclax (VEN) + azacitidine (AZA) and VEN + low-dose cytarabine (LDAC) compared with AZA, LDAC, and decitabine monotherapies and best supportive care (BSC) in adults with untreated acute myeloid leukemia ineligible for intensive chemotherapy. METHODS: A systematic literature review and feasibility assessment was conducted to select phase III randomized controlled trials for inclusion in the NMA. Complete remission + complete remission with incomplete blood count recovery and overall survival (OS) were compared using a Bayesian fixed-effects NMA. Treatments were ranked using surface under the cumulative ranking curves (SUCRAs) with higher values indicating a higher likelihood of being effective. RESULTS: A total of 1140 patients across 5 trials were included. VEN + LDAC (SUCRA 91.4%) and VEN + AZA (87.5%) were the highest ranked treatments for complete remission + complete remission with incomplete blood count recovery. VEN + LDAC was associated significantly higher response rates versus AZA (odds ratio 5.64), LDAC (6.39), and BSC (23.28). VEN + AZA was also associated significantly higher response rates than AZA (5.06), LDAC (5.74), and BSC (20.68). In terms of OS, VEN + AZA (SUCRA: 95.2%) and VEN + LDAC (75.9%) were the highest ranked treatments. VEN + AZA was associated with significant improvements in OS compared with AZA (hazard ratio 0.66), LDAC (0.57), and BSC (0.37), and VEN + LDAC was associated with significant improvements in OS compared with LDAC (0.70) and BSC (0.46). CONCLUSIONS: VEN + AZA and VEN + LDAC demonstrated improved efficacy compared with alternative therapies among treatment-naive patients with acute myeloid leukemia ineligible for intensive chemotherapy.

Ontogenetic transitions, biomechanical trade-offs and macroevolution of scyphozoan medusae swimming patterns.

Ephyrae, the early stages of scyphozoan jellyfish, possess a conserved morphology among species. However, ontogenetic transitions lead to morphologically different shapes among scyphozoan lineages, with important consequences for swimming biomechanics, bioenergetics and ecology. We used high-speed imaging to analyse biomechanical and kinematic variables of swimming in 17 species of Scyphozoa (1 Coronatae, 8 "Semaeostomeae" and 8 Rhizostomeae) at different developmental stages. Swimming kinematics of early ephyrae were similar, in general, but differences related to major lineages emerged through development. Rhizostomeae medusae have more prolate bells, shorter pulse cycles and higher swimming performances. Medusae of "Semaeostomeae", in turn, have more variable bell shapes and most species had lower swimming performances. Despite these differences, both groups travelled the same distance per pulse suggesting that each pulse is hydrodynamically similar. Therefore, higher swimming velocities are achieved in species with higher pulsation frequencies. Our results suggest that medusae of Rhizostomeae and "Semaeostomeae" have evolved bell kinematics with different optimized traits, rhizostomes optimize rapid fluid processing, through faster pulsations, while "semaeostomes" optimize swimming efficiency, through longer interpulse intervals that enhance mechanisms of passive energy recapture.

High Doses of Caffeine Increase Muscle Strength and Calcium Release in the Plasma of Recreationally Trained Men.

The effects of acute caffeine supplementation on muscular strength remain unclear. We examined the effects of two different doses of caffeine on muscle strength and calcium in plasma compared to placebo using a crossover, randomized, double-blind, placebo-controlled design. Twenty-one (n = 21) recreationally resistance-trained participants were randomly assigned into three experimental conditions: 6 mg·kg bw−1 of caffeine (CF6); 8 mg·kg bw−1 of caffeine (CF8); or placebo (PLA), with a 7-day washout period between conditions. Muscular strength assessments were made for both upper (bench press) and lower body muscles (squat and deadlift). Calcium release in plasma was measured on five different occasions. Bench press (CF8: 100.1 ± 1.9 kg; PLA: 94.2 ± 2.5 kg), deadlift (CF8: 132.8 ± 3.5 kg; PLA: 120.7 ± 5.7 kg), and squat (CF8: 130.1 ± 4.9 kg; PLA 119.4 ± 5.4 kg) strength were all significantly (p < 0.001) improved in CF8 compared to PLA. Calcium release in plasma was significantly increased in CF8, whereas no changes were observed in CF6 or PLA. Overall, 8 mg·kg bw−1 of caffeine appears to be an effective dose to optimize upper and lower body muscular strength and calcium release in recreationally trained participants.

Acute effect of passive heat exposure on markers of cardiometabolic function in adults with type 2 diabetes mellitus.

Heat therapy is a promising strategy to improve cardiometabolic health. This study evaluated the acute physiological responses to hot water immersion in adults with type 2 diabetes mellitus (T2DM). On separate days in randomized order, 13 adults with T2DM [8 males/5 females, 62 ± 12 yr, body mass index (BMI): 30.1 ± 4.6 kg/m2] were immersed in thermoneutral (34°C, 90 min) or hot (41°C, core temperature ≥38.5°C for 60 min) water. Insulin sensitivity was quantified via the minimal oral model during an oral glucose tolerance test (OGTT) performed 60 min after immersion. Brachial artery flow-mediated dilation (FMD) and reactive hyperemia were evaluated before and 40 min after immersion. Blood samples were drawn to quantify protein concentrations and mRNA levels of HSP70 and HSP90, and circulating concentrations of cytokines. Relative to thermoneutral water immersion, hot water immersion increased core temperature (+1.66°C [+1.47, +1.87], P < 0.01), heart rate (+34 beats/min [+24, +44], P < 0.01), antegrade shear rate (+96 s-1 [+57, +134], P < 0.01), and IL-6 (+1.38 pg/mL [+0.31, +2.45], P = 0.01). Hot water immersion did not exert an acute change in insulin sensitivity (-0.3 dL/kg/min/µU/mL [-0.9, +0.2], P = 0.18), FMD (-1.0% [-3.6, +1.6], P = 0.56), peak (+0.36 mL/min/mmHg [-0.71, +1.43], P = 0.64), and total (+0.11 mL/min/mmHg × min [-0.46, +0.68], P = 0.87) reactive hyperemia. There was also no change in eHSP70 (P = 0.64), iHSP70 (P = 0.06), eHSP90 (P = 0.80), iHSP90 (P = 0.51), IL1-RA (P = 0.11), GLP-1 (P = 0.59), and NF-κB (P = 0.56) after hot water immersion. The physiological responses elicited by hot water immersion do not acutely improve markers of cardiometabolic function in adults with T2DM.NEW & NOTEWORTHY Heat therapy has been shown to improve markers of cardiometabolic health in preclinical and clinical studies. However, the effects of heat therapy in individuals with type 2 diabetes mellitus (T2DM) remain understudied. We examined the acute effect of hot water immersion on glucose tolerance, flow-mediated dilation, reactive hyperemia, inflammatory markers, and heat shock proteins in adults with T2DM. Hot water immersion did not acutely improve the markers studied.

Reduced Dose of Beta-Alanine Is Sufficient to Maintain Performance in Repeated Sprints.

ABSTRACT: Zandona, BA, Ramos, RA, de Oliveira, CdS, McAnulty, SR, Ferreira, LHB, Smolarek, AC, Enes, AAN, Urbinati, KMdSS, Aragon, AA, Schoenfeld, BJ, and de Souza Junior, TP. Reduced Dose of Beta-Alanine Is Sufficient to Maintain Performance in Repeated Sprints. J Strength Cond Res 36(6): 1636-1642, 2022-Beta-alanine (BA) supplementation has been shown to be effective in improving physical performance by increasing carnosine concentration. However, it is still necessary to know the effect of a maintenance dose on performance. Thus, this study aimed to investigate the effects of a maintenance dose of BA supplementation on performance. Forty-four anaerobically trained men with 23.9 ± 3.8 years of age, 176.0 ± 0.05 cm height, 81.2 ± 7.5 kg body mass, and 15.5 ± 2.9% of body fat performed a cycle ergometer test consisting of 4 sprints of 30 s with 4 minutes of active recovery. The study comprised 3 phases: (a) presupplementation, (b) supplementation with 6.4 g·d-1 BA or placebo, and (c) postsupplementation with a maintenance dose of 1.2 g·d-1 of BA or interruption of supplementation. Data were analyzed using generalized estimated equations with a priori 0.05 level of significance. The placebo group and interruption group presented a lower power (7.28 ± 0.66 and 7.71 ± 0.42 W·kg-1 vs. 8.04 ± 0.84 and 9.25 ± 1.18 W·kg-1, respectively; p < 0.05) during the third sprint in postsupplementation, whereas the maintenance group maintained the required power (7.47 ± 1.03 vs. 8.74 ± 1.07 W·kg-1; p > 0.05). The placebo group also presented higher percentage of fatigue (44.5% ± 12.3 and 44.8% ± 7.7 vs. 37.6 ± 7.2%; p = 0.021) and higher subjective perception of exertion (8.92 ± 0.90 vs. 8.00 ± 1.60; p = 0.028). Therefore, the maintenance dose of 1.2 g·d-1 BA was effective in maintaining performance, whereas a reduction in performance was observed after supplementation interruption.

Measurement of IgE to hazelnut allergen components cannot replace hazelnut challenge in Dutch adults.

BACKGROUND: Component-resolved diagnostics (CRD) help predict hazelnut allergy (HA) in children, but are of unknown diagnostic value in adults. This study aimed to evaluate the diagnostic accuracy of IgE to hazelnut extract and components in adults. METHODS: A Dutch population of consecutively presenting adults suspected of HA, who underwent a double-blind placebo-controlled food challenge, were included. Serum IgE to hazelnut extract and Cor a 1, 8, 9, and 14 was measured on ImmunoCAP. Diagnostic accuracy was assessed by area under the curve (AUC) analysis. RESULTS: Of 89 patients undergoing challenge, 46 had challenge-confirmed HA: 17 based on objective and 29 based on subjective symptoms. At commonly applied cutoffs 0.1 and 0.35 kUA /L, high sensitivity was observed for IgE to hazelnut extract and Cor a 1 (range 85-91%), and high specificity for IgE to Cor a 8, 9 and 14 (range 77-95%). However, the AUCs for hazelnut extract and components were too low for accurate prediction of HA (range 0.50-0.56). Combining hazelnut extract and component IgE measurements did not significantly improve accuracy. Higher IgE levels to Cor a 9 and 14 were tentatively associated with HA with objective symptoms, but the corresponding AUCs still only reached 0.68 and 0.63, respectively. CONCLUSIONS: Although hazelnut allergic adults are generally sensitized to hazelnut extract and Cor a 1, and hazelnut tolerant adults are usually not sensitized to Cor a 8, 9, or 14, challenge testing is still needed to accurately discriminate between presence and absence of HA in adults from a birch-endemic country.

High-throughput drug screening identifies the ATR-CHK1 pathway as a therapeutic vulnerability of CALR mutated hematopoietic cells.

Mutations of calreticulin (CALR) are the second most prevalent driver mutations in essential thrombocythemia and primary myelofibrosis. To identify potential targeted therapies for CALR mutated myeloproliferative neoplasms, we searched for small molecules that selectively inhibit the growth of CALR mutated cells using high-throughput drug screening. We investigated 89 172 compounds using isogenic cell lines carrying CALR mutations and identified synthetic lethality with compounds targeting the ATR-CHK1 pathway. The selective inhibitory effect of these compounds was validated in a co-culture assay of CALR mutated and wild-type cells. Of the tested compounds, CHK1 inhibitors potently depleted CALR mutated cells, allowing wild-type cell dominance in the co-culture over time. Neither CALR deficient cells nor JAK2V617F mutated cells showed hypersensitivity to ATR-CHK1 inhibition, thus suggesting specificity for the oncogenic activation by the mutant CALR. CHK1 inhibitors induced replication stress in CALR mutated cells revealed by elevated pan-nuclear staining for γH2AX and hyperphosphorylation of RPA2. This was accompanied by S-phase cell cycle arrest due to incomplete DNA replication. Transcriptomic and phosphoproteomic analyses revealed a replication stress signature caused by oncogenic CALR, suggesting an intrinsic vulnerability to CHK1 perturbation. This study reveals the ATR-CHK1 pathway as a potential therapeutic target in CALR mutated hematopoietic cells.

Neurotoxicity of Olindias sambaquiensis and Chiropsalmus quadrumanus extracts in sympathetic nervous system.

Cnidarians are equipped with nematocysts, which are specialized organelles used to inoculate venom during prey capturing and defense. Their venoms are rich in toxins and a potential source of bioactive compounds, however, poorly explored so far. In this work, the activity of the methanolic extracts from the hydromedusa Olindias sambaquiensis and the cubozoan jellyfish Chiropsalmus quadrumanus were studied in sympathetic neurotransmission. For that, bisected rat vas deferens - a classic model of sympathetic neurotransmission - were incubated with the extracts for further myographic and histopathological analysis. The O. sambaquiensis extract, at 0.1 µg/mL, facilitated the neurogenic contractions of the noradrenergic-rich epididymal portion, while reducing the noradrenaline (NA) potency, which suggests an interaction with postsynaptic α1-adrenoceptors. On the other hand, a higher concentration (1 µg/mL) leads to time- and frequency-dependent blockade of nerve-evoked contractions without significantly changing the response to exogenous NA. In turn, the C. quadrumanus extract at 0.1 µg/mL induced blockade of nerve-evoked noradrenergic contractions while reducing the potency to exogenous NA. Both extracts did not affect the purinergic neurotransmission or induce muscle damages. Our results demonstrate that O. sambaquiensis and C. quadrumanus extracts significantly interfere with the noradrenergic neurotransmission without altering purinergic response or smooth muscle structure on rat vas deferens. Such results bring to light the pharmacological potential of O. sambaquiensis and C. quadrumanus molecules for therapeutics focusing on noradrenergic neurotransmission.

First description of wild-collected ephyrae of Lychnorhiza lucerna (Cnidaria, Scyphozoa).

Ephyrae are the young scyphozoan jellyfishes that usually passes unnoticed, whereas their adult counterparts play major ecological roles and can negatively affect economic activities when they occur in high densities. We describe, for the first time, wild ephyrae of Lychnorhiza lucerna (Scyphozoa, Rhizostomeae) from the Patos Lagoon Estuary, Southern Brazil. A total of 10 ephyrae were found in salinities between 12 and 33 and temperatures between 16 and 27°C. The presence of digitata, eight oral arms and serrated tips on marginal lobes allowed species determination. Wild ephyrae were morphologically identical to laboratory-cultivated individuals. The youngest individual was about one to two days old, and the most developed one, between 12 and 14 days old. Recruitment of L. lucerna probably initiated during warmer months (December until February) because nine out of ten individuals were found in high temperature (> 20° C) and salinity (> 30) waters. On the other hand, a mid-winter occurrence of a single ephyra (T=16° C, S= 12) demonstrates that the species may support a considerable range of variation in the physical environment. We reinforce the importance of long-term studies to provide information about the species coupling with seasonal cycles and the dynamics of estuarine and coastal areas.

Melatonin and Depression: A Translational Perspective From Animal Models to Clinical Studies.

Daily rhythm of melatonin synchronizes the body to the light/dark environmental cycle. Several hypotheses have been raised to understand the intersections between melatonin and depression, in which changes in rest-activity and sleep patterns are prominent. This review describes key experimental and clinical evidence that link melatonin with the etiopathology and symptomatology of depressive states, its role in the follow up of therapeutic response to antidepressants, as well as the clinical evidence of melatonin as MDD treatment. Melatonin, as an internal temporal cue contributing to circadian organization and best studied in the context of circadian misalignment, is also implicated in neuroplasticity. The monoaminergic systems that underly MDD and melatonin production overlap. In addition, the urinary metabolite 6-sulfatoxymelatonin (aMT6) has been proposed as biomarker for antidepressant responders, by revealing whether the blockage of noradrenaline uptake has taken place within 24 h from the first antidepressant dose. Even though animal models show benefits from melatonin supplementation on depressive-like behavior, clinical evidence is inconsistent vis-à-vis prophylactic or therapeutic benefits of melatonin or melatonin agonists in depression. We argue that the study of melatonin in MDD or other psychiatric disorders must take into account the specificities of melatonin as an integrating molecule, inextricably linked to entrainment, metabolism, immunity, neurotransmission, and cell homeostasis.

Identification and Purification of Novel Low-Molecular-Weight Lupine Allergens as Components for Personalized Diagnostics.

Lupine flour is a valuable food due to its favorable nutritional properties. In spite of its allergenic potential, its use is increasing. Three lupine species, Lupinus angustifolius, L. luteus, and L. albus are relevant for human nutrition. The aim of this study is to clarify whether the species differ with regard to their allergen composition and whether anaphylaxis marker allergens could be identified in lupine. Patients with the following characteristics were included: lupine allergy, suspected lupine allergy, lupine sensitization only, and peanut allergy. Lupine sensitization was detected via CAP-FEIA (ImmunoCAP) and skin prick test. Protein, DNA and expressed sequence tag (EST) databases were queried for lupine proteins homologous to already known legume allergens. Different extraction methods applied on seeds from all species were examined by SDS-PAGE and screened by immunoblotting for IgE-binding proteins. The extracts underwent different and successive chromatography methods. Low-molecular-weight components were purified and investigated for IgE-reactivity. Proteomics revealed a molecular diversity of the three species, which was confirmed when investigated for IgE-reactivity. Three new allergens, L. albus profilin, L. angustifolius and L. luteus lipid transfer protein (LTP), were identified. LTP as a potential marker allergen for severity is a valuable additional candidate for molecular allergy diagnostic tests.

Study on the transfusion representation by nurses and midwives at the university hospital of Brest.

INTRODUCTION: Every day, large numbers of patients benefit from effective transfusion substitution therapy, through transfusion procedures that are generally safe and reliable. This care practice is complex, due to its history through the ages, ethical aspects linked to the donation of blood from one human to another, and the procedures and protocols linked to it. Nurses are a key link in the transfusion chain and are directly affected by the procedures implemented to limit transfusion risks. In this research study, we studied the nurses' and midwives' representations of transfusion, to evaluate their possible effects on transfusion practices. METHODOLOGY: With the aid of the various actors involved in transfusion, we developed and tested a questionnaire, which was then sent to 690 professionals in 69 care units. RESULTS: In total, 491 questionnaires were analyzed, corresponding to a response rate of 71%. The data collected revealed a strong feeling of responsibility among the healthcare staff questioned, with great attention paid to transfusion safety. The risk to the patient is very much taken into account by these professionals, who consider transfusion to be a healthcare practice unlike any other, generating a certain stress that affected all those questioned, regardless of the number of years they had been in practice, but was tempered by knowledge. CONCLUSION: This survey shows that nurses and midwives are very aware of the risks of transfusion to the patient, and that they take these risks into account with the same diligence throughout their careers. It would be useful to carry out semi-directed interviews to refine some of these results further.