Clustering of 24H movement behaviors associated with clinic blood pressure in older adults: a cross-sectional study.

Physical activity (PA), sedentary behavior (SB), and sleep duration are known to have an individual effect on clinic blood pressure (BP) of older adults. However, whether different patterns of these so-called movement behaviors over the 24h-cycle on BP remains poorly investigated. The study aimed to identify movement behavior patterns associated with clinic BP among older adults with chronic diseases. Cross-sectional study with 238 older adults (80.3% female; mean age 68.8 ± 6.6) with at least one chronic disease. PA, SB, and sleep duration were measured by a triaxial accelerometer. Clinic systolic BP (SBP) and diastolic BP (DBP) were obtained through an automated method following standard procedures. Non-hierarchical K-means cluster and linear regression modeling were employed to identify the clusters of movement behaviors and to examine the associations. Two clusters were identified [active and non-sedentary, n = 103 (i.e., sufficient sleep duration, higher LPA and MVPA, and lower SB) and sedentary and inactive, n = 135 (i.e., sufficient sleep duration, lower LPA and MVPA, and higher SB). Active and non-sedentary older adults presented lower systolic BP compared to sedentary and inactive ones, even after adjustments for sociodemographic and clinical characteristics (ß = 6.356; CI 95% from 0.932 to 11.779; P = 0.022). No associations were found for diastolic BP. In conclusion, higher PA and lower SB were associated with lower systolic BP in older adults with chronic diseases. However, sleep duration did not modify this association. Therefore, interventions focusing on concomitantly increasing PA levels and reducing SB should be the priority for controlling blood pressure.

Are There Differences Among Evidence-Based Psychotherapies for Treating Different DSM-5 PTSD Symptom Clusters? A Systematic Review and Meta-analysis of Controlled Clinical Trials.

ABSTRACT: Posttraumatic stress disorder (PTSD) is a heterogeneous disease defined by four Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) symptom clusters: reexperiencing, avoidance, negative alterations in cognitions and mood, and hyperarousal. There are effective evidence-based psychotherapies (EBPs) for PTSD. However, given the variety of PTSD clinical presentations, we conducted the first meta-analysis investigating whether DSM-5 PTSD symptom clusters show different responses to EBPs. We systematically reviewed the literature for controlled clinical trials in five databases, performed a meta-analysis, and evaluated the methodological quality of the studies. We screened 633 studies and included seven. Three showed high risk, two showed some concerns, and one showed a low risk of bias. The symptom clusters do not seem to respond differently to EBPs (SMD cluster B: -0.40; 95% confidence interval [CI], -0.87 to 0.08; cluster C: -0.49; 95% CI, -0.90 to -0.08; cluster D: -0.44; 95% CI, -0.94 to 0.05; cluster E: -0.54; 95% CI, -1.07 to -0.0), even when analyzed by the therapeutic focuses. The findings dovetail nicely with the network theory of PTSD symptom, as although it is a heterogeneous disorder, the EBPs seem to promote a kind of cascade of symptom improvement.

Exosome Liberation by Human Neutrophils under L-Amino Acid Oxidase of Calloselasma rhodostoma Venom Action.

L-Amino acid oxidase (LAAO) is an enzyme found in snake venom that has multifaceted effects, including the generation of hydrogen peroxide (H2O2) during oxidative reactions, leading to various biological and pharmacological outcomes such as apoptosis, cytotoxicity, modulation of platelet aggregation, hemorrhage, and neutrophil activation. Human neutrophils respond to LAAO by enhancing chemotaxis, and phagocytosis, and releasing reactive oxygen species (ROS) and pro-inflammatory mediators. Exosomes cellular nanovesicles play vital roles in intercellular communication, including immune responses. This study investigates the impact of Calloselasma rhodostoma snake venom-derived LAAO (Cr-LAAO) on human neutrophil exosome release, including activation patterns, exosome formation, and content. Neutrophils isolated from healthy donors were stimulated with Cr-LAAO (100 µg/mL) for 3 h, followed by exosome isolation and analysis. Results show that Cr-LAAO induces the release of exosomes with distinct protein content compared to the negative control. Proteomic analysis reveals proteins related to the regulation of immune responses and blood coagulation. This study uncovers Cr-LAAO's ability to activate human neutrophils, leading to exosome release and facilitating intercellular communication, offering insights into potential therapeutic approaches for inflammatory and immunological disorders.

Quantum chemical investigation of predominant conformation of the antibiotic azithromycin in water and DMSO solutions: thermodynamic and NMR analysis.

Azithromycin (AZM) is a macrolide-type antibiotic used to prevent and treat serious infections (mycobacteria or MAC) that significantly inhibit bacterial growth. Knowledge of the predominant conformation in solution is of fundamental importance for advancing our understanding of the intermolecular interactions of AZM with biological targets. We report an extensive density functional theory (DFT) study of plausible AZM structures in solution considering implicit and explicit solvent effects. The best match between the experimental and theoretical nuclear magnetic resonance (NMR) profiles was used to assign the preferred conformer in solution, which was supported by the thermodynamic analysis. Among the 15 distinct AZM structures, conformer M14, having a short intramolecular C6-OH … N H-bond, is predicted to be dominant in water and dimethyl sulfoxide (DMSO) solutions. The results indicated that the X-ray structure backbone is mostly conserved in solution, showing that large flexible molecules with several possible conformations may assume a preferential spatial orientation in solution, which is the molecular structure that ultimately interacts with biological targets.

Impaired Decision-Making Capacity in the Elderly King David (c. 1040-970 BCE): Was Hypothyroidism the Underlying Cause?

It has been suggested in the medical literature that in the last period of his life King David (c. 1040-970 BCE) suffered from dementia, osteoporosis, hyperparathyroidism, Parkinson's disease, autonomic neuropathy, major depression, and malignancy. The goal of this study was to identify, based on the "Succession Narrative (SN)," a historically objective section of the Old Testament, the clinical syndrome presented by King David and to determine whether an impaired decision making capacity may have been manipulated by his courtiers to influence his succession's politics. The "SN" indicates that besides forgetfulness and trouble in thinking, King David suffered from marked cold intolerance and sexual dysfunction. The symptom triad consisting of cognitive impairment, cold intolerance, and sexual dysfunction is more strongly suggestive of hypothyroidism than of any other diagnoses proposed in the medical literature so far. We hypothesized that hypothyroidism was the underlying cause of the elderly King David's clinical picture and that his sometimes troubled thinking was successfully manipulated by the courtiers to favor his son Solomon's accession to the throne, with profound historical consequences.

Synthesis and Activity of 2-Acyl-cyclohexane-1,3-dione Congeners Derived from Peperomia Natural Products against the Plant p-Hydroxyphenylpyruvate Dioxygenase Herbicidal Molecular Target Site.

Plastoquinone is a key electron carrier in photosynthesis and an essential cofactor for the biosynthesis of carotenoids. p-Hydroxyphenylpyruvate dioxygenase (HPPD) is a vital enzymatic step in plastoquinone biosynthesis that is the target of triketone herbicides, such as those derived from the pharmacophore backbone of the natural product leptospermone. In this work, the inhibitory activity of a series of 2-acyl-cyclohexane-1,3-diones congeners derived from Peperomia natural products was tested on plant HPPD. The most active compound was a 2-acyl-cyclohexane-1,3-dione with a C11 alkyl side chain (5d; I50app: 0.18 ± 0.02 µM) that was slightly more potent than the commercial triketone herbicide sulcotrione (I50app: 0.25 ± 0.02 µM). QSAR analysis and docking studies were performed to further characterize the key structural features imparting activity. A 1,3-dione feature was required for inhibition of HPPD. Molecules with a side chain of 11 carbons were found to be optimal for inhibition, while the presence of a double bond, hydroxy, or methyl beyond the required structural features on the cyclohexane ring generally decreased HPPD inhibiting activity.

An investigation of the predominant structure of antibiotic azithromycin in chloroform solution through NMR and thermodynamic analysis.

Azithromycin (AZM) is a well-known macrolide-type antibiotic that has been used in the treatment of infections and inflammations. Knowledge of the predominant molecular structure in solution is a prerequisite for an understanding of the interactions of the drug in biological media. Experimental structural determination can be carried out for samples in solid-state (X-ray diffraction technique) and gas phase (electron diffraction experiment). In solution, spectroscopic methods can be used to extract valuable information which combined with quantum chemical calculations can lead to the determination of the preferred molecular structures to be observed when a given solute is dissolved in each solvent. That is precisely the aim of this work. We used experimental NMR chemical shift data (in CDCl3) as a reference for comparison with Density Functional Theory (DFT) NMR calculations, with geometry optimized having as guess input two crystallographic structures available in the literature with the configuration of all chiral carbon atoms inverted, named here A and B. The Polarizable Continuum Model (PCM) was used to describe the solvent effects (chloroform) including five explicit CHCl3 solvent molecules, which we believe can account for short and long-range solute-solvent interactions. Analysis of calculated thermodynamic, NMR chemical shift, MAE (Mean Absolute Error), and spin-spin coupling constant values revealed that both supposable C3R-C5S (named M2-A) and C3S-C5R (named M2-B) structures are equally probable to exist in chloroform solution. In addition, we found that the heavy atoms' conformation is reasonably similar in the solid-state and chloroform solution; however, regarding the OH groups, the spatial orientations are rather different with intramolecular OH⋯N and OH⋯O hydrogen bonds present in solution and with some of them being absent in the X-ray structure probably due to crystal packing effects.

Preparation, cytotoxic activity and DNA interaction studies of new platinum(II) complexes with 1,10-phenanthroline and 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives.

This work describes the synthesis, characterization and in vitro anticancer activity of two platinum(II) complexes of the type [Pt(L1)2(1,10-phen)] 1 and [Pt(L2)2(1,10-phen)] 2, where L1 = 5-heptyl-1,3,4-oxadiazole-2-(3H)-thione, L2 = 5-nonyl-1,3,4-oxadiazole-2-(3H)-thione and 1,10-phen = 1,10-phenanthroline. As to the structure of these complexes, the X-ray structural analysis of 1 indicates that the geometry around the platinum(II) ion is distorted square-planar, where two 5-alkyl-1,3,4-oxadiazol-2-thione derivatives coordinate a platinum(II) ion through the sulfur atom. A chelating bidentate phenanthroline molecule completes the coordination sphere. We tested these complexes in two breast cancer cell lines, namely, MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). In both cells, the most lipophilic platinum compound, complex 2, was more active than cisplatin, one of the most widely used anticancer drugs nowadays. DNA binding studies indicated that such complexes are able to bind to ct-DNA with Kb values of 104 M-1. According to data from dichroism circular and fluorescence spectroscopy, these complexes appear to bind to the DNA in a non-intercalative, probably via minor groove. Molecular docking followed by semiempirical simulations indicated that these complexes showed favorable interactions with the minor groove of the double helix of ct-DNA in an A-T rich region. Thereafter, flow cytometry analysis showed that complex 2 induced apoptosis and necrosis in MCF-7 cells.

Dynamics of action of a Lys-49 and an Asp-49 PLA2s on inflammasome NLRP3 activation in murine macrophages.

Phospholipases A2 (PLA2s) are proteins found in snake venoms with hemolytic, anticoagulant, myotoxic, edematogenic, bactericidal and inflammatory actions. In Bothrops jararacussu snake venom were isolated a Lys49-PLA2 (BthTX-I) and an Asp49-PLA2 (BthTX-II) with myotoxic and inflammatory actions. Both PLA2s can activate the NLRP3 inflammasome, an intracytoplasmic platform that recognizes molecules released when tissue is damaged liberating IL-1ß that contributes to the inflammatory response observed in envenoming. The dynamic of action of BthTX-I and BthTX-II in both thioglycollate (TG)-elicited macrophages and C2C12 myoblasts and the involvement of EP1 and EP2 receptors, and PGE2 in NLRP3 inflammasome activation were evaluated. Both toxins induced PGE2 liberation and inflammasome components (NLRP3, Caspase-1, ASC, IL-1ß, and IL18), IL-6, P2X7, COX-1, COX-2, EP2 and EP4 gene expression in TG-elicited macrophages but not in C2C12 myoblasts. EP2 (PF04418948) and EP4 (GW627368X) inhibitors abolished this effect. Both PLA2s also induced NLRP3 inflammasome protein expression that was abolished with the inhibitors used. Immunofluorescence and IL-1ß assays confirmed the NLRP3 activation in TG-elicited macrophages with the participation of both EP2 and EP4 receptors confirming their involvement in this effect. All in all, BthTX-I and BthTX-II activate macrophages and induce the NLRP3 inflammasome complex activation with the participation of the PGE2 via COX pathway and EP2 and EP4, both PGE2 receptors, contributing to the local inflammatory effects observed in envenoming.

Validity and reliability of the Baecke questionnaire against accelerometer-measured physical activity in community dwelling adults according to educational level.

Baecke questionnaire have been widely used to assess physical activity. However, the role of educational level on validity and reliability of Baecke questionnaire is still not stablished, being a factor that can potentially influence the accuracy of self-reported measures. The present study aimed to verify the validity and reliability of Baecke questionnaire for the measurement of physical activity in community dwelling adults according to education level. The sample included 251 adults (42.4±17.0 years, 55% of women). Physical activity was self-reported by Baecke questionnaire and objectively measured by accelerometer. The education level (EL) was classified by years of study into low (<8 years), medium (8-11 years) and high (>11 years). A 7-day test-retest reliability was analyzed by intraclass correlation coefficient. The relationship, agreement and validity of the Baecke questionnaire against accelerometry were analyzed by Spearman's correlation, Kappa index, and ROC curve, respectively. The reliability of Baecke questionnaire were r = 0.97 (high EL), r = 0.78 (medium EL), and r = 0.68 (low EL). Sensitivity and specificity were 77% and 71% in high EL, 54% and 80% in medium EL and 33% and 89% in the low EL. Baecke questionnaire proved to be reliable and a valid measurement of habitual physical activity in adults with medium and high EL.

Inflammasome NLRP3 activation induced by Convulxin, a C-type lectin-like isolated from Crotalus durissus terrificus snake venom.

Convulxin (CVX), a C-type lectin-like protein isolated from the venom of the snake species, Crotalus durissus terrificus, stimulates platelet aggregation by acting as a collagen receptor agonist for glycoprotein VI found in the platelets. The effect of CVX on platelets has been studied, but its effect on human peripheral blood mononuclear cells (PBMCs) remains unclear. Given the significance of PBMCs in inflammation, this study explored the effect of CVX on PBMCs, specifically regarding NLRP3 inflammasome activation by assessing cell viability, ability to induce cell proliferation, reactive oxygen species (ROS) and nitric oxide production, interleukin (IL)-2 and IL-10 secretion, NLRP3 complex activation, and the role of C-type lectin-like receptors (CTLRs) in these. CVX was not toxic to PBMCs at the investigated concentrations and did not increase PBMC growth or IL-2 release; however, CVX induced IL-10 release and ROS generation via monocyte activation. It also activated the NLRP3 complex, resulting in IL-1ß induction. Furthermore, the interaction between CVX and Dectin-2, a CTLR, induced IL-10 production. CVX interaction with CTLR has been demonstrated by laminarin therapy. Because of the involvement of residues near the Dectin-2 carbohydrate-recognition site, the generation of ROS resulted in inflammasome activation and IL-1ß secretion. Overall, this work helps elucidate the function of CVX in immune system cells.

Case Report: Depression × dementia with Lewy bodies in the elderly: The importance of differential diagnosis.

Background: Dementia is a clinical syndrome which is more common in elderly people. Dementia with Lewy bodies (LBD) is not so rare in elderly people, with cognitive impairment in about 30% over age 65. The clinical picture is characterized by fluctuation in cognitive functions, recurrent, well-formed, detailed visual hallucinations, and Parkinsonism, with rigidity, tremor, bradykinesia, and slurred speech. Case presentation: We present a case report of LBD in a 73-year-old retired teacher, which a initial wrong diagnosis of refractory depression for at least 3 years. We also conduct a review of recent works on theme. Conclusion: LBD diagnosis can be neglected for years, with a legal and clinical issues to patients and their families. Detailed medical research, including differential diagnosis, are very necessary on those cases, specially when they are called refractory. We encourage new research and adequate clinical training to prevent damage.

Tonic Immobility is Associated with PTSD Symptoms in Traumatized Adolescents.

PURPOSE: Growing evidence suggests that peritraumatic tonic immobility, an involuntary defensive response that involves extreme physical immobility and the perceived inability to escape, is a significant predictor of post-traumatic stress disorder (PTSD) symptomatology. However, this issue has not been specifically addressed in adolescents. Here, we investigated whether tonic immobility response experienced during the worst childhood or adolescent trauma is associated with PTSD symptom severity in a non-clinical student sample. METHODS: The sample was composed of students in 9th grade who were attending public and private schools. Symptoms of post-traumatic stress and tonic immobility were assessed using questionnaires. We performed bivariate and multivariate negative binomial regressions to examine whether tonic immobility was associated with PTSD symptomatology after controlling for confounders (peritraumatic dissociation, peritraumatic panic reactions, gender, age and time since trauma). RESULTS: We found an association between tonic immobility and PTSD symptom severity, even after controlling for confounders. Therefore, tonic immobility is associated with PTSD symptoms in trauma-exposed adolescents. CONCLUSION: These findings highlight tonic immobility as a possible risk factor that could be used to provide direction for more targeted trauma interventions for individuals, particularly those at risk for developing PTSD. Therefore, it contributes to preventing and reducing the psychiatric burden in adolescence and later in life.

Photobiomodulation induces murine macrophages polarization toward M2 phenotype.

Photobiomodulation using light-emitting diode (LED) treatment has analgesic and anti-inflammatory effects which can be an effective therapeutic associated with serum therapy for local treatment of snakebites. Here we explored the effects of LED treatment on isolated macrophage under Bothrops jararacussu venom. Results showed that LED induced IL-6 and TNF-α genes down-regulation and, TGF and ARG1 genes up-regulation which indicates a polarization of macrophages to an M2 phenotype contributing to both tissue repair and resolution of inflammation.