Revisiting Biginelli-like reactions: solvent effects, mechanisms, biological applications and correction of several literature reports.

This study critically reevaluates reported Biginelli-like reactions using a Kamlet-Abboud-Taft-based solvent effect model. Surprisingly, structural misassignments were discovered in certain multicomponent reactions, leading to the identification of pseudo three-component derivatives instead of the expected MCR adducts. Attempts to replicate literature conditions failed, prompting reconsideration of the described MCRs and proposed mechanisms. Electrospray ionization (tandem) mass spectrometry, NMR, melting points, elemental analyses and single-crystal X-ray analysis exposed inaccuracies in reported MCRs and allowed for the proposition of a complete catalytic cycle. Biological investigations using both pure and "contaminated" derivatives revealed distinctive features in assessed bioassays. A new cellular action mechanism was unveiled for a one obtained pseudo three-component adduct, suggesting similarity with the known dihydropyrimidinone Monastrol as Eg5 inhibitors, disrupting mitosis by forming monoastral mitotic spindles. Docking studies and RMSD analyses supported this hypothesis. The findings described herein underscore the necessity for a critical reexamination and potential corrections of structural assignments in several reports. This work emphasizes the significance of rigorous characterization and critical evaluation in synthetic chemistry, urging a careful reassessment of reported synthesis and biological activities associated with these compounds.

Single-Nucleotide Polymorphisms Associated with Mercury Levels and Neurological Symptoms: An Overview.

Mercury (Hg) pollution is a global public health concern because of its adverse effects on the environment and health. Single-nucleotide polymorphisms (SNPs) have been associated with Hg levels and outcomes. The aim of this review was to describe the research and discuss the evidence on the genetic susceptibility of Hg-exposed individuals to the development of neurocognitive disorders. A systematic review was performed to identify the genes/SNPs associated with Hg toxicokinetics and that, therefore, affect neurological function in exposed populations. Observational and experimental studies were identified by screening three databases. Thirteen articles were included (quality score 82-100%) and 8124 individuals were evaluated. Hg exposure was mainly fish consumption (77%) and, in 31% of the studies, the Hg levels exceeded the reference limits. Genetic susceptibility to higher Hg levels and neurotoxicity risk in Hg poisoning were associated with eight (ALAD rs1800435, CYP3A4 rs2740574, CYP3A5 rs776746, CYP3A7 rs2257401, GSTP1 rs1695, MT1A rs8052394, MT1M rs2270836, and MT4 rs11643815) and three (MT1A rs8052394, MT1M rs2270837, and MT2A rs10636) SNPs, respectively, and rs8052394 was associated with both outcomes. The MT1A rs8052394 SNP may be used as a susceptibility biomarker to identify individuals at greater risk for higher Hg levels and the development of neurocognitive disorders in metal-exposed populations.

Cannabidiol induces systemic analgesia through activation of the PI3Kγ/nNOS/NO/KATP signaling pathway in neuropathic mice. A KATP channel S-nitrosylation-dependent mechanism.

BACKGROUND: Cannabidiol (CBD) is the second most abundant pharmacologically active component present in Cannabis sp. Unlike Δ-9-tetrahydrocannabinol (THC), it has no psychotomimetic effects and has recently received significant interest from the scientific community due to its potential to treat anxiety and epilepsy. CBD has excellent anti-inflammatory potential and can be used to treat some types of inflammatory and neuropathic pain. In this context, the present study aimed to evaluate the analgesic mechanism of cannabidiol administered systemically for the treatment of neuropathic pain and determine the endogenous mechanisms involved with this analgesia. METHODS: Neuropathic pain was induced by sciatic nerve constriction surgery, and the nociceptive threshold was measured using the paw compression test in mice. RESULTS: CBD produced dose-dependent antinociception after intraperitoneal injection. Selective inhibition of PI3Kγ dose-dependently reversed CBD-induced antinociception. Selective inhibition of nNOS enzymes reversed the antinociception induced by CBD, while selective inhibition of iNOS and eNOS did not alter this antinociception. However, the inhibition of cGMP production by guanylyl cyclase did not alter CBD-mediated antinociception, but selective blockade of ATP-sensitive K+ channels dose-dependently reversed CBD-induced antinociception. Inhibition of S-nitrosylation dose-dependently and completely reversed CBD-mediated antinociception. CONCLUSION: Cannabidiol has an antinociceptive effect when administered systemically and this effect is mediated by the activation of PI3Kγ as well as by nitric oxide and subsequent direct S-nitrosylation of KATP channels on peripheral nociceptors.

Micellar solution of [223Ra]RaCl2: Reaching renal excretion, potent efficacy in osteoblastic osteosarcoma in PDX model, biochemistry alterations and pharmacokinetics.

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.

A benchmark of optimization solvers for genome-scale metabolic modeling of organisms and communities.

Genome-scale metabolic modeling is a powerful framework for predicting metabolic phenotypes of any organism with an annotated genome. For two decades, this framework has been used for the rational design of microbial cell factories. In the last decade, the range of applications has exploded, and new frontiers have emerged, including the study of the gut microbiome and its health implications and the role of microbial communities in global ecosystems. However, all the critical steps in this framework, from model construction to simulation, require the use of powerful linear optimization solvers, with the choice often relying on commercial solvers for their well-known computational efficiency. In this work, I benchmark a total of six solvers (two commercial and four open source) and measure their performance to solve linear and mixed-integer linear problems of increasing complexity. Although commercial solvers are still the fastest, at least two open-source solvers show comparable performance. These results show that genome-scale metabolic modeling does not need to be hindered by commercial licensing schemes and can become a truly open science framework for solving urgent societal challenges.IMPORTANCEModeling the metabolism of organisms and communities allows for computational exploration of their metabolic capabilities and testing their response to genetic and environmental perturbations. This holds the potential to address multiple societal issues related to human health and the environment. One of the current limitations is the use of commercial optimization solvers with restrictive licenses for academic and non-academic use. This work compares the performance of several commercial and open-source solvers to solve some of the most complex problems in the field. Benchmarking results show that, although commercial solvers are indeed faster, some of the open-source options can also efficiently tackle the hardest problems, showing great promise for the development of open science applications.

Nitric oxide and potassium channels but not opioid and cannabinoid receptors mediate tramadol-induced peripheral antinociception in rat model of paw pressure withdrawal.

Tramadol, an analgesic classified as an "atypical opioid", exhibits both opioid and non-opioid mechanisms of action. This study aimed to explore these mechanisms, specifically the opioid-, cannabinoid-, nitric oxide-, and potassium channel-based mechanisms, which contribute to the peripheral antinociception effect of tramadol, in an experimental rat model. The nociceptive threshold was determined using paw pressure withdrawal. To examine the mechanisms of action, several substances were administered intraplantarly: naloxone, a non-selective opioid antagonist (50 µg/paw); AM251 (80 µg/paw) and AM630 (100 µg/paw) as the selective antagonists for types 1 and 2 cannabinoid receptors, respectively; nitric oxide synthase inhibitors L-NOArg, L-NIO, L-NPA, and L-NIL (24 µg/paw); and the enzyme inhibitors of guanylatocyclase and phosphodiesterase of cGMP, ODQ, and zaprinast. Additionally, potassium channel blockers glibenclamide, tetraethylammonium, dequalinium, and paxillin were used. The results showed that opioid and cannabinoid receptor antagonists did not reverse tramadol's effects. L-NOarg, L-NIO, and L-NPA partially reversed antinociception, while ODQ completely reversed, and zaprinast enhanced tramadol's antinociception effect. Notably, glibenclamide blocked tramadol's antinociception in a dose-dependent manner. These findings suggest that tramadol's peripheral antinociception effect is likely mediated by the nitrergic pathway and sensitive ATP potassium channels, rather than the opioid and cannabinoid pathways.

Percepção de gestantes quanto à atuação do enfermeiro no pré-natal / Perception of pregnant women regarding the performance of nurses in prenatal care / Percepción de las gestantes sobre la actuación del enfermero en el prenatal

Objetivo: identificar a percepção de gestantes quanto à atuação do enfermeiro no pré-natal. Método: pesquisa fenomenológica que entrevistou 10 gestantes de um município de Minas Gerais, Brasil. Os depoimentos foram organizados em categorias e analisados segundo a fenomenologia social de Alfred Schütz e literatura temática. Resultados: emergiram as categorias "Assistência centrada em ações técnicas", "Fragilidade na comunicação entre enfermeiro e gestante" e a expectativa de "orientações qualificadas desenvolvidas mediante atividades coletivas". Considerações finais: os resultados suscitam a necessidade de valorizar os aspectos subjetivos e comunicacionais no pré-natal, para além das ações técnicas, com vistas a efetivação do vínculo entre os atores, ampliação da adesão e da qualidade do pré-natal. Para tal, recomenda-se atividades de educação permanente

Objective: to identify the perception of pregnant women regarding the role of nurses in prenatal care. Method: phenomenological research that interviewed 10 pregnant women in a city in Minas Gerais, Brazil. The statements were organized into categories and analyzed according to Alfred Schütz's social phenomenology and thematic literature. Results: the categories "Care centered on technical actions", "Fragility in communication between nurse and pregnant woman" and the expectation of "qualified guidelines developed through collective activities" emerged. Final considerations: the results raise the need to value subjective and communicational aspects in prenatal care, in addition to technical actions, with a view to establishing the bond between actors, expanding adherence and quality of prenatal care. To this end, continuing education activities are recommended

Objetivos: identificar la percepción de las gestantes sobre el papel del enfermero en el prenatal. Método: investigación fenomenológica que entrevistó a 10 mujeres embarazadas en una ciudad de Minas Gerais, Brasil. Los enunciados fueron organizados en categorías y analizados según la fenomenología social y la literatura temática de Alfred Schütz. Resultados: surgieron las categorías "Cuidado centrado en acciones técnicas", "Fragilidad en la comunicación entre enfermero y gestante" y la expectativa de "orientaciones calificadas desarrolladas a través de actividades colectivas". Consideraciones finales: los resultados plantean la necesidad de valorar los aspectos subjetivos y comunicacionales en el prenatal, además de las acciones técnicas, con miras a establecer el vínculo entre los actores, ampliando la adherencia y la calidad del prenatal. Para ello, se recomiendan actividades de educación continua

Systematization of perioperative nursing care in robotic surgery: instrument validation.

OBJECTIVE: To develop and validate an instrument to assist in the systematization of perioperative nursing care in robotic surgery. METHODS: Methodological study developed in four phases: content survey; textual elaboration; content validation by the group of expert judges and target audience; and elaboration of the electronic instrument layout. RESULTS: Eleven expert judges and seven evaluators of the target audience participated. For validation, the Content Validity Index (CVI) was used with a 0.78 cutoff point. The instrument total CVI after evaluation was 0.90 by the expert judges and 0.88 by the target audience. CONCLUSION: The tool built was proved satisfactory for the systematization of perioperative nursing care. The instrument construction was based on the updated scientific literature and validated by the expert judges and target audience.

Microbial interactions shape cheese flavour formation.

Cheese fermentation and flavour formation are the result of complex biochemical reactions driven by the activity of multiple microorganisms. Here, we studied the roles of microbial interactions in flavour formation in a year-long Cheddar cheese making process, using a commercial starter culture containing Streptococcus thermophilus and Lactococcus strains. By using an experimental strategy whereby certain strains were left out from the starter culture, we show that S. thermophilus has a crucial role in boosting Lactococcus growth and shaping flavour compound profile. Controlled milk fermentations with systematic exclusion of single Lactococcus strains, combined with genomics, genome-scale metabolic modelling, and metatranscriptomics, indicated that S. thermophilus proteolytic activity relieves nitrogen limitation for Lactococcus and boosts de novo nucleotide biosynthesis. While S. thermophilus had large contribution to the flavour profile, Lactococcus cremoris also played a role by limiting diacetyl and acetoin formation, which otherwise results in an off-flavour when in excess. This off-flavour control could be attributed to the metabolic re-routing of citrate by L. cremoris from diacetyl and acetoin towards α-ketoglutarate. Further, closely related Lactococcus lactis strains exhibited different interaction patterns with S. thermophilus, highlighting the significance of strain specificity in cheese making. Our results highlight the crucial roles of competitive and cooperative microbial interactions in shaping cheese flavour profile.

Kisspeptin (Kp-10) inhibits in vitro osteogenic differentiation of multipotent mesenchymal stromal cells extracted from the bone marrow of adult rats.

Kisspeptin (Kp-10) is a neuropeptide that binds to GPR54 receptors, exerting several functions mainly in the nervous and reproductive systems of the body. However, its effects and mechanisms of action on the skeletal system remain poorly understood. This study evaluated the effects of different concentrations of Kp-10 on in vitro osteogenic differentiation of multipotent mesenchymal stromal cells (MSCs) extracted from the bone marrow (BM) of adult Wistar rats. Two-month-old female rats were euthanized to extract BM from long bones to obtain MSCs. Four experimental groups were established in vitro: a control and Kp-10 at concentrations of 0.01, 0.05 and, 0.1 µg/mL. After induction of osteogenic differentiation, cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide (MTT) assay, alkaline phosphatase activity, collagen synthesis, percentage of area covered by MSCs/field and mineralized nodules/field, and immunocytochemistry of the GPR54 receptor tests. Furthermore, evaluation of gene transcripts for type I collagen, Runx-2, Bmp-2, bone sialoprotein, osteocalcin and osteopontin was performed using real-time RT-qPCR. It was observed that MSCs expressed GPR54 receptor to which Kp-10 binds during osteogenic differentiation, promoting a negative effect on osteogenic differentiation. This effect was observed at all the Kp-10 concentrations in a concentration-dependent manner, characterized by a decrease in the activity of alkaline phosphatase, collagen synthesis, mineralized nodules, and decreased expression of gene transcripts for type I collagen, osteocalcin, osteopontin, and Runx-2. Thus, Kp-10 inhibits in vitro osteogenic differentiation of MSCs extracted from the BM of adult Wistar rats.

Concomitant dual-site tDCS and dark chocolate improve cognitive and endurance performance following cognitive effort under hypoxia: a randomized controlled trial.

Ten male cyclists were randomized into four experimental conditions in this randomized, cross-over, double-blind, and sham-controlled study to test the combined effect of acute dark chocolate (DC) ingestion and anodal concurrent dual-site transcranial direct current stimulation (a-tDCS) targeting M1 and left DLPFC on cognitive and whole-body endurance performance in hypoxia after performing a cognitive task. Two hours before the sessions, chocolate was consumed. After arriving at the lab, participants completed an incongruent Stroop task for 30 min in hypoxia (O2 = 13%) to induce mental fatigue, followed by 20 min of tDCS (2 mA) in hypoxia. Then, in hypoxia, they performed a time-to-exhaustion task (TTE) while measuring physiological and psychophysiological responses. Cognitive performance was measured at baseline, after the Stroop task, and during and after TTE. TTE in 'DC + a-tDCS' was significantly longer than in 'white chocolate (WC) + a-tDCS' and WC + sham-tDCS'. The vastus medialis muscle electromyography amplitude was significantly higher in 'DC + a-tDCS' and 'DC + sham-tDCS' than in 'WC + sh-tDCS'. During and after the TTE, choice reaction time was significantly lower in 'DC + a-tDCS' compared to 'WC + sh-tDCS'. Other physiological or psychophysiological variables showed no significant differences. The concurrent use of acute DC consumption and dual-site a-tDCS might improve cognitive and endurance performance in hypoxia.

Euterpe oleracea extract (açaí) exhibits cardioprotective effects after chemotherapy treatment in a breast cancer model.

BACKGROUND: Açaí, a Brazilian native fruit, has already been demonstrated to play a role in the progress of breast cancer and cardiotoxicity promoted by chemotherapy agents. Thus, the present study aimed to evaluate the combined use of açaí and the FAC-D chemotherapy protocol in a breast cancer model in vivo. METHODS: Mammary carcinogenesis was induced in thirty female Wistar rats by subcutaneous injection of 25 mg/kg 7,12-dimethylbenzanthracene (DMBA) in the mammary gland. After sixty days, the rats were randomized into two groups: treated with 200 mg/kg of either açaí extract or vehicle, via gastric tube for 45 consecutive days. The FAC-D protocol was initiated after 90 days of induction by intraperitoneal injection for 3 cycles with a 7-day break each. After treatment, blood was collected for haematological and biochemical analyses, and tumours were collected for macroscopic and histological analyses. In the same way, heart, liver, and kidney samples were also collected for macroscopic and histological analyses. RESULTS: Breast cancer was found as a cystic mass with a fibrotic pattern in the mammary gland. The histological analysis showed an invasive carcinoma area in both groups; however, in the saline group, there was a higher presence of inflammatory clusters. No difference was observed regarding body weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea in either group. However, açaí treatment decreased creatine kinase (CK), creatine kinase MB (CKMB), troponin I and C-reactive protein levels and increased the number of neutrophils and monocytes. Heart histopathology showed normal myocardium in the açaí treatment, while the saline group presented higher toxicity effects with loss of architecture of cardiac tissue. Furthermore, the açaí treatment presented greater collagen distribution, increased hydroxyproline concentration and lower H2AX immunostaining in the heart samples. CONCLUSION: Açaí decreased the number of inflammatory cells in the tumor environment and exhibited protection against chemotherapy drug cardiotoxicity with an increased immune response in animals. Thus, açaí can be considered a promising low-cost therapeutic treatment that can be used in association with chemotherapy agents to avoid heart damage.

Effect of tDCS targeting the M1 or left DLPFC on physical performance, psychophysiological responses, and cognitive function in repeated all-out cycling: a randomized controlled trial.

BACKGROUND: Despite reporting the positive effects of transcranial direct current stimulation (tDCS) on endurance performance, very few studies have investigated its efficacy in anaerobic short all-out activities. Moreover, there is still no consensus on which brain areas could provide the most favorable effects on different performance modalities. Accordingly, this study aimed to investigate the effects of anodal tDCS (a-tDCS) targeting the primary motor cortex (M1) or left dorsolateral prefrontal cortex (DLPFC) on physical performance, psychophysiological responses, and cognitive function in repeated all-out cycling. METHODS: In this randomized, crossover, and double-blind study, 15 healthy physically active men underwent a-tDCS targeting M1 or the left DLPFC or sham tDCS in separate days before performing three bouts of all-out 30s cycling anaerobic test. a-tDCS was applied using 2 mA for 20 min. Peak power, mean power, fatigue index, and EMG of the quadriceps muscles were measured during each bout. Heart rate, perceived exertion, affective valence, and arousal were recorded two minutes after each bout. Color-word Stroop test and choice reaction time were measured at baseline and after the whole anaerobic test. RESULTS: Neither tDCS montage significantly changed peak power, mean power, fatigue index, heart rate, affective valence, arousal, and choice reaction time (p> 0.05). a-tDCS over DLPFC significantly lowered RPE of the first bout (compared to sham; p=0.048, Δ=-12.5%) and third bout compared to the M1 (p=0.047, Δ=-12.38%) and sham (p=0.003, Δ=-10.5%), increased EMG of the Vastus Lateralis muscle during the second (p=0.016, Δ= +40.3%) and third bout (p=0.016, Δ= +42.1%) compared to sham, and improved the score of color-word Stroop test after the repeated all-out task (p=0.04, Δ= +147%). The qualitative affective response (valence and arousal) was also higher under the M1 and DLPFC compared to the sham. CONCLUSION: We concluded that tDCS targeting M1 or DLPFC does not improve repeated anaerobic performance. However, the positive effect of DLPFC montage on RPE, EMG, qualitative affective responses, and cognitive function is promising and paves the path for future research using different tDCS montages to see any possible effects on anaerobic performance. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Razi University (IR.RAZI.REC.1400.023) and registered in the Iranian Registry of Clinical Trials (IRCT id: IRCT20210617051606N5; Registration Date: 04/02/2022).

(Ro)vibrational Spectroscopic Constants, Lifetime and QTAIM Evaluation of Fullerene Dimers Stability.

The iconic caged shape of fullerenes gives rise to a series of unique chemical and physical properties; hence a deeper understanding of the attractive and repulsive forces between two buckyballs can bring detrimental information about the structural stability of such complexes, providing significant data applicable for several studies. The potential energy curves for the interaction of multiple van der Waals buckyball complexes with increasing mass were theoretically obtained within the DFT framework at ωB97xD/6-31G(d) compound model. These potential energy curves were employed to estimate the spectroscopic constants and the lifetime of the fullerene complexes with the Discrete Variable Representation and with the Dunham approaches. It was revealed that both methods are compatible in determining the rovibrational structure of the dimers and that they are genuinely stable, i.e., long-lived complexes. To further inquire into the nature of such interaction, Bader's QTAIM approach was applied. QTAIM descriptors indicate that the interactions of these closed-shell systems are dominated by weak van der Waals forces. This non-covalent interaction character was confirmed by the RDG analysis scheme. Indirectly, QTAIM also allowed us to confirm the stability of the non-covalent bonded fullerene dimers. Our lifetime calculations have shown that the studied dimers are stable for more than 1 ps, which increases accordingly with the number of carbon atoms.

Influence of interleukin-8 polymorphism on endometriosis-related pelvic pain.

Endometriosis presents a pro-inflammatory microenvironment influenced by cytokines, such as interleukin (IL)-8, which expression may be influenced by genetic polymorphisms. Therefore, we aimed to investigate the role of interleukin (IL)-8 rs4073 polymorphism in endometriosis' development and its related symptoms. A case-control study was conducted with 207 women with endometriosis and 193 healthy controls. Polymorphism was genotyped using a TaqMan validated assay. Associations were evaluated by binary logistic regression, using odds ratios (OR) and 95 % confidence intervals (CI), and P ≤ 0.05 was considered significant. Cases were younger (36 ± 6.8 versus 39 ± 8.4) and had lower body mass index (26.5 ± 5.3 versus 35.7 ± 6.3 Kg/m2) than controls (P < 0.001). Higher prevalence of symptoms and infertility was observed in cases, compared to controls (P < 0.001). Minor allele frequencies of IL-8 rs4073 (T) were 42.3 % and 39.9 % for cases and controls, respectively, and no associations were found between IL and 8 rs4073 polymorphism and endometriosis' prevalence or staging. However, the polymorphism was associated with chronic pelvic pain among cases (OR = 0.54; 95 %CI = 0.29-0.98). The IL-8 rs4073A > T polymorphism may contribute to lower IL-8 expression and, consequently, decrease endometriosis-related pelvic pain. These findings can support the early diagnosis of endometriosis' painful symptoms, preventing its complications, and allowing an individualized treatment.

Intensity-Dependent Influence of Interoceptive Accuracy on Psychophysiological Responses During Aerobic Exercise in Physically Inactive Men.

We aimed to investigate the influence of interoceptive accuracy on affective valence, arousal, and ratings of perceived exertion (RPE) during 20 minutes of aerobic exercise at both moderate and heavy intensity among physically inactive men. We divided our participant sample into men with poor heartbeat perception (PHP, n = 13) and good heartbeat perception (GHP, n = 15), based on their cardioceptive accuracy. We measured their heart rate reserve (%HRreserve), perceived affective valence (Feeling Scale; +5/-5), perceived arousal (Felt Arousal Scale, 0-6), and ratings of perceived effort (RPE; Borg scale 6-20) every five minutes during an exercise session on a bicycle ergometer. During moderate-intensity aerobic exercise, the GHP group presented a greater decline in affective valence (p = 0.010; d = 1.06) and a greater increase in RPE (p = 0.004; d = 1.20) compared to the PHP group, with no group differences in %HRreserve (p = 0.590) and arousal (p = 0.629). Psychophysiological and physiological responses to the heavy-intensity aerobic exercise were not different between groups. We concluded that the influence of interoceptive accuracy on psychophysiological responses during submaximal fixed-intensity aerobic exercise was intensity-dependent in these physically inactive men.

The vicious cycle of psychopathology and stressful life events: A meta-analytic review testing the stress generation model.

Stress generation theory initially posited that depression elevates risk for some stressful events (i.e., dependent events) but not others (i.e., independent events). This preregistered meta-analytic review examined whether stress generation occurs transdiagnostically by examining 95 longitudinal studies with 38,228 participants (537 total effect sizes) from over 30 years of research. Our multilevel meta-analyses found evidence of stress generation across a broad range of psychopathology, as evidenced by significantly larger prospective effects for dependent (overall psychopathology: r = .23) than independent (overall psychopathology: r = .10) stress. We also identified unique patterns of effects across specific types of psychopathology. For example, effects were larger for depression than anxiety. Furthermore, effects were sometimes larger in studies with younger participants, shorter time lags between assessments, checklist measures of stress, and for interpersonal stressors. Finally, a multilevel meta-analytic structural equation model suggested that dependent stress exacerbates psychopathology symptoms over time (ß = .04), possibly contributing to chronicity. Interventions targeting the prevention of stress generation may mitigate chronic psychopathology. Conclusions of this study are limited by the predominance of depression effect sizes in the literature and our review of only English language articles. On the other hand, the findings are strengthened by rigorous inclusion criteria, lack of publication bias, and absence of moderating effects by publication year. The latter underscores the replicability of the stress generation effect over the last 30 years. Taken together, the review provides robust evidence that stress generation is a cross-diagnostic phenomenon that contributes to a vicious cycle of increasing stress and psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).