Search

The presented study aims to assess the mechanical behaviour of the anterior abdominal wall based on an in vivo experiment on humans. Full-field measurement of abdominal wall displacement during changes of intra-abdominal pressure is performed using a digital image correlation (DIC) system. Continuous measurement in time enables the observation of changes in the strain field during breathing. The understanding of the mechanical behaviour of a living human abdominal wall is important for the proper design of surgical meshes used for ventral hernia repair, which was also a motivation for the research presented below. The research refers to the strain field of a loaded abdominal wall and presents the evolution of principal strains and their directions in the case of 12 subjects, 8 male and 4 female. Peritoneal dialysis procedure allows for the measurement of intra-abdominal pressure after fluid introduction. High variability among patients is observed, also in terms of principal strain direction. Subjects exhibit intra-abdominal pressure of values from 11 to 21 cmH 2 O. However, the strain values are not strongly correlated with the pressure value, indicating variability of material properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In response to shortcomings with the current diagnostic classification system for mental health disorders, such as poor validity and reliability of categorical diagnoses, the National Institute of Mental Health proposed the Research Domain Criteria (RDoC) initiative to move towards a dimensional approach using translational research. The current study examined associations between measures of behaviors, cognitions, and mental health symptoms and how they overlap in the Negative Valence Systems (NVS) domain. Specifically, we examined how the Self-Reports unit of analysis reflects the RDoC NVS constructs of acute threat, potential threat, sustained threat, frustrative nonreward, and loss. The overall goal was to identify additional self-report measures that reflect these constructs. Participants, two student samples and two community samples (total N = 1,509), completed online self-reported measures. Questionnaire total and subscale scores were submitted to a principal-axis factor analysis with Promax rotation separately for each sample. For both student samples and one community sample six-factor solutions emerged reflecting major aspects of the RDoC NVS and positive valence systems, particularly acute threat (i.e., fear/panic), potential threat (i.e., inhibition/worry), sustained threat (i.e., chronic stress), loss (i.e., low well-being), frustrative nonreward (i.e., reactive aggression), and reduced behavioral activation. The second community sample differed in that fear/panic and frustration/anger was combined in a general distress factor. Recommendations for additional NVS self-report markers are discussed., (Copyright © 2022. Published by Elsevier Ltd.)

The study concerns mechanical behaviour of a living human abdominal wall. A better mechanical understanding of a human abdominal wall and recognition of its material properties is required to find mechanically compatible surgical meshes to significantly improve the treatment of ventral hernias. A non-invasive methodology, based on in vivo optical measurements is proposed to determine strains of abdominal wall corresponding to a known intraabdominal pressure. The measurement is performed in the course of a standard procedure of peritoneal dialysis. A dedicated experimental stand is designed for the experiment. The photogrammetric technique is employed to recover the three-dimensional surface geometry of the anterior abdominal wall at the initial and terminal instants of the dialysis. This corresponds to two deformation states, before and after filling the abdominal cavity with dialysis fluid. The study provides information on strain fields of living human abdominal wall. The inquiry is aimed at principal strains and their directions, observed at the level from -10% to 17%. The intraabdominal pressure related to the amount of introduced dialysis fluid measured within the medical procedure covers the range 11-18.5 cmH 2 O. The methodology leads to the deformation state of the abdominal wall according to the corresponding loading conditions. Therefore, the study is a step towards an identification of mechanical properties of living human abdominal wall., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach.

T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic neoplasm. Differentiation stage and immune-effector functions of the underlying tumor cell are insufficiently characterized. Constitutive activation of the T-cell leukemia 1A (TCL1A) oncogene distinguishes the (pre)leukemic cell from regular postthymic T cells. We assessed activation-response patterns of the T-PLL lymphocyte and interrogated the modulatory impact by TCL1A. Immunophenotypic and gene expression profiles revealed a unique spectrum of memory-type differentiation of T-PLL with predominant central-memory stages and frequent noncanonical patterns. Virtually all T-PLL expressed a T-cell receptor (TCR) and/or CD28-coreceptor without overrepresentation of specific TCR clonotypes. The highly activated leukemic cells also revealed losses of negative-regulatory TCR coreceptors (eg, CTLA4). TCR stimulation of T-PLL cells evoked higher-than-normal cell-cycle transition and profiles of cytokine release that resembled those of normal memory T cells. More activated phenotypes and higher TCL1A correlated with inferior clinical outcomes. TCL1A was linked to the marked resistance of T-PLL to activation- and FAS-induced cell death. Enforced TCL1A enhanced phospho-activation of TCR kinases, second-messenger generation, and JAK/STAT or NFAT transcriptional responses. This reduced the input thresholds for IL-2 secretion in a sensitizer-like fashion. Mice of TCL1A-initiated protracted T-PLL development resembled such features. When equipped with epitope-defined TCRs or chimeric antigen receptors, these Lckpr-hTCL1Atg T cells gained a leukemogenic growth advantage in scenarios of receptor stimulation. Overall, we propose a model of T-PLL pathogenesis in which TCL1A enhances TCR signals and drives the accumulation of death-resistant memory-type cells that use amplified low-level stimulatory input, and whose loss of negative coregulators additionally maintains their activated state. Treatment rationales are provided by combined interception in TCR and survival signaling., (© 2020 by The American Society of Hematology.)

Changes in metabolites composition can reflect currently present pathological processes in a living organism and constitute a basis for diagnosis and treatment improvements. Thus, the multiplatform metabolomics approach was applied for the investigation of molecular mechanisms of chronic kidney disease (CKD) progression. The high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-TOF-MS) and gas chromatography coupled with triple quadrupole mass spectrometry (GC-QqQ/MS) serum metabolic fingerprinting followed by uni- and multivariate statistical analysis was carried out to determine metabolic pattern differentiating CKD patients and healthy controls. Furthermore, metabolites changes between stage 3 and 4 of the disease, as well as health status were investigated. The progression of the disease was found to be related to alterations in acylcarnitine, amino acid, lysophospholipid and carbohydrate metabolism. Elevated levels of serum acylcarnitines, sugar alcohols, and organic acids, as well as decreased levels of lysophospholipids, and amino acids, were found to be statistically significant for CKD progression. The obtained results confirm the utility of metabolomics approach as a tool for an explanation of molecular processes underlying CKD development., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Experiential avoidance (also referred to as acceptance or psychological flexibility) is a core construct of third-wave behavior therapies. It is the tendency to avoid uncomfortable thoughts or feelings, even when doing so has negative long-term consequences. In order for developments in experiential avoidance and third-wave behavior therapies to continue, it is imperative to examine the construct validity of the most widely used measures of this construct, the Acceptance and Action Questionnaire-II (AAQ-II) and the Multidimensional Experiential Avoidance Questionnaire (MEAQ). In Amazon's Mechanical Turk (N = 1,052) and college (N = 364) samples, we evaluated the construct validity of these measures. The AAQ-II demonstrated suboptimal patterns of convergent and discriminant validity with measures of neuroticism/negative affect (Big Five Inventory, Big Five Aspects Scale, Positive and Negative Affect Schedule), the MEAQ, and mindfulness (Five Factor Mindfulness Questionnaire). In contrast, the MEAQ demonstrated optimal convergent and discriminant validity. Factor analyses at the scale, subscale, and item levels demonstrated that the AAQ-II loads with indicators of neuroticism/negative affect and not with other constructs at the core of third-wave behavior therapies. In contrast, the MEAQ loads on factors with mindfulness or forms its own factors. These findings suggest the AAQ-II functions as a measure of neuroticism/negative affect, whereas the MEAQ functions as an indicator of experiential avoidance. These findings have substantial implications for research on experiential avoidance and third-wave behavior therapies. Therefore, in order to improve the theory, research, and practice of third-wave behavior therapies, we recommend using the MEAQ to assess experiential avoidance., (Copyright © 2017. Published by Elsevier Ltd.)

1,3-Dipolar cycloadditions of 2-deoxy-D-ribose-derived L-threo five-membered cyclic nitrone to α,β-unsaturated γ- and δ-lactones were investigated. Cycloadducts obtained from δ-lactones, after NO bond cleavage, opening of the lactone ring, and protection of hydroxyl groups were subjected to β-lactam ring formation by using Mukaiyama's salt. Cycloadducts from γ-lactones subjected to the same reaction sequence undergo β-elimination of a water molecule to provide pyrrolidine-substituted unsaturated γ-lactones., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Synthesis of glycosyl hydroperoxides derived from 2,3,4,6-tetra-O-benzyl-d-glucopyranose and 2,3,4,6-di-O-isopropylidene-d-mannofuranose was performed via a Schmidt's imidate intermediate with hydrogen peroxide in an ethyl ether solution in the presence of an acid catalyst. Separation of the α- and β-anomers of the glycosyl hydroperoxides was achieved by chromatography., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Obsessive-compulsive disorder (OCD) is a heterogeneous condition, comprised of multiple symptom domains. This study used aggregate composite scales representing three core OCD dimensions (Checking, Cleaning, and Rituals), as well as Hoarding, to examine the discriminant validity, diagnostic specificity, and predictive ability of OCD symptom scales. The core OCD scales demonstrated strong patterns of convergent and discriminant validity - suggesting that these dimensions are distinct from other self-reported symptoms - whereas hoarding symptoms correlated just as strongly with OCD and non-OCD symptoms in most analyses. Across analyses, our results indicated that Checking is a particularly strong, specific marker of OCD diagnosis, whereas the specificity of Cleaning and Hoarding to OCD was less strong. Finally, the OCD Checking scale was the only significant predictor of OCD diagnosis in logistic regression analyses. Results are discussed with regard to the importance of assessing OCD symptom dimensions separately and implications for classification., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aim: Accelerated atherosclerosis is a characteristic feature of chronic kidney disease (CKD). CD36 is a scavenger receptor which contributes to foam cell formation, an early crucial step in atherosclerosis development. Recently, a soluble form of CD36 (sCD36) has been discovered. The aim of the study was to develop an ELISA method for quantitative sCD36 evaluation and to measure it in a cohort of CKD stage 5 patients., Method: A novel monoclonal antibody-based sandwich ELISA for sCD36 evaluation was developed and verified by repeated optimization procedures. Serum concentration of sCD36 was then analyzed in a cohort of 228 CKD stage 5 patients prior to dialysis initiation. Additionally, samples from a control group of 73 healthy, age and gender-matched subjects were evaluated., Results: The novel CD36 ELISA assay had a recovery of at least 90%, and intra- and inter-assay variability of 6 and 11%, respectively. Concentration of serum sCD36 in CKD patients was significantly increased as compared to controls, and associated with the use of HMG-CoA reductase inhibitors (statins) and the presence of diabetes mellitus (DM). Patients above the 75th percentile of sCD36 concentration were at increased risk of 3-year cardiovascular mortality, as compared to the rest of the cohort [HR 2.85 (1.09-7.59) p=0.03]., Conclusion: For the first time, sCD36 was assessed quantitatively in a group of patients and showed associations with DM, CKD, and statin use. Furthermore, the concentration of sCD36 predicted cardiovascular mortality in CKD stage 5 patients., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Oxidation of 3,4,6-tri-O-benzyl-2-deoxy-d-glucose and d-galactose or their t-butyl glycosides to the corresponding glycosyl hydroperoxides can be performed with hydrogen peroxide in the presence of an acid catalyst. Several reaction conditions and their influence on the effectiveness of the oxidation are discussed. Separation of the α - and β-anomers of the glycosyl hydroperoxides was achieved through mixed peroxide formation by reaction of the hydroperoxide group with 2-methoxypropene and subsequent deprotection., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The 1,3-dipolar cycloaddition of the cyclic nitrone derived from tartaric acid and (S)-5-hydroxymethyl-2(5H)-furanone leads to the single adduct 7 which can be transformed into the 3-epi-1-homo-casuarine via a reaction sequence involving reduction of the lactone moiety and N-O bond hydrogenolysis, followed by intramolecular alkylation of the nitrogen atom. The adduct 7 can also be used in the synthesis of 1-methyl- or 3-methyl analogues of 3-epi-casuarine.

The 1,3-dipolar cycloaddition of cyclic nitrone derived from tartaric acid and (S)-5-hydroxymethyl-2(5H)-furanone leads to a single adduct which was transformed into 2,6-dihydroxyhastanecine via reaction sequence involving reduction of the lactone moiety, glycolic cleavage of the terminal diol, and the N-O hydrogenolysis followed by the intramolecular alkylation of the nitrogen atom.

Background & Aims: Muscle wasting is considered the best marker of protein-energy wasting in end-stage renal disease (ESRD). We tested the usefulness of a simple observer subjective muscle atrophy (MA) grading in relation to morbidity and mortality in ESRD patients., Methods: In two different ESRD cohorts (265 incident patients starting dialysis and 221 prevalent hemodialysis patients), each patient's degree of MA was visually graded by a trained nurse on a scale from 1 to 4 as part of the subjective global assessment. This score was confronted with inflammatory and nutritional indexes as well as objective measurements of muscle atrophy. Patients were then prospectively followed for up to four or six years, depending on the cohort., Results: Thirty percent of the incident and 39% of the prevalent patients presented signs of MA. Across worsening MA scale, nutritional and anthropometric markers of muscle loss were incrementally poorer. Inflammation markers as well as the proportion of women became progressively higher. Female sex, presence of cardiovascular disease, inflammation and low insulin-like growth factor-1 levels were associated with increased significant odd ratios of MA in each cohort. After adjustment for age, sex, inflammation, diabetes, cardiovascular disease, glomerular filtration rate and/or time on hemodialysis, the hazard ratio of death for moderate/severe MA was 2.62 (95% CI: 1.34, 5.13; p=0.001) and 3.04 (95% CI: 1.61, 5.71; p=0.0001) in the incident and prevalent cohorts respectively., Conclusion: Increased MA is more common in female dialysis patients and associated with inflammation, poor nutritional and anthropometric status, as well as a 3-fold increased 4-6 year mortality. Our data support the use of frequent MA and/or nutritional assessments in the clinical practice.

DFT calculations were carried out on axially and equatorially oriented 2-hydroperoxy and 2-peroxy tetrahydropyran, cyclohexyl hydroperoxide, hydroperoxides of 2,3-unsaturated hexapyranoses, and hydroperoxides of OMe and OBn substituted derivatives of 2-deoxy-glucopyranose and 2-deoxy-galactopyranose to investigate the anomeric and exo-anomeric effects of these groups. The structure and energy of the conformers were calculated at the B3LYP/6-311++G** level. Calculations showed that the peroxy anion group exhibits a strong anomeric effect, comparable in magnitude to the methoxy group, and that the anomeric effect of the hydroperoxy group is similar to the hydroxyl group. These results revealed that hydroperoxy and peroxy anion groups display an exo-anomeric effect, but the orientation around the C1-O1 bond is also affected by hydrogen bonding and electrostatic interactions.

Sterol regulatory element-binding protein-2 (SREBP-2) is a transcription factor regarded as the main regulator of cholesterol homeostasis. Therefore, increased level of SREBP-2 could be responsible for hypercholesterolemia, which is observed in experimental chronic renal failure (CRF). This study was designed primary to evaluate the impact of experimental CRF (5/6 nephrectomy model) on rat liver SREBP-2 gene expression. In CRF rats, a twofold increase in SREBP-2 mRNA level, as well as in mature SREBP-2 protein abundance was found, when compared to control animals. It was associated with enhanced activity and mRNA abundance of liver HMG-CoA reductase, a rate-limiting enzyme for cholesterol biosynthesis. A twofold increase in liver cholesterologenesis rate was also noted. We conclude that experimental CRF is associated with increased liver SREBP-2 gene expression. This is probably the cause for enhanced HMG-CoA reductase gene expression and, consequently, for increase in liver cholesterol synthesis in CRF rats. Despite increased SREBP-2 gene expression we found LDL-receptor mRNA level to be lower than in controls, suggesting SREBP-2 independent mechanisms of LDL-receptor transcriptional regulation in CRF rats. Enhanced cholesterol synthesis and decreased LDL-receptor mRNA level are probably responsible for an almost fourfold increase in serum cholesterol concentration in CRF rats.

The 1,3-dipolar cycloaddition of a five-membered cyclic nitrone derived from malic acid and unsaturated D-threo-hexonolactone leads to a single adduct, which was transformed into 1-homoaustraline via a reaction sequence involving rearrangement of the six-membered lactone ring into the five-membered one, removal of the terminal carbon atom from the sugar chain, reduction of the lactone fragment into triol, protection of primary hydroxy groups, mesylation of the secondary one, cleavage of the N-O bond, and the intramolecular alkylation of the nitrogen atom.

The [2 + 2] cycloaddition of chlorosulfonyl isocyanate to (Z)-4-O-propenyl ethers 16, 17, 29 and 30 proceeds with an excellent stereoselectivity in the case of ether 16 and with moderate stereoselectivity in remaining cases. Adducts were transformed into corresponding oxacephams: 37 in the first case, a mixture of 37/40 in the second and third case, and a mixture of 50/51 in the last case. In all instances addition to the si-re side of the olefin dominates. Oxacephams 41 and 52 with opposite R-configuration at the bridgehead carbon C-5a can be obtained by the alternate methodology based on the alkylation of nitrogen in 4-vinyloxyazetidin-2-one by protected 6-O-triflate 24 or 25, followed by cyclization via intramolecular displacement of the vinyloxy group. Compounds 37, 40, 41, 50, 51 and 52 constitute a convenient entry leading to polyfunctionalized oxacephams., (Copyright 2002 Elsevier Science Ltd.)

(1aR,5aR,5bS,6S,7S)-6,7-Di-tert-butoxy-5-oxo-pyrrolidino[1,2-b]isoxazolidino[4,5-c]tetrahydropyran (8) prepared by (1,3)-dipolar cycloaddition of the cyclic nitrone 6 derived from tartaric acid to 5,6-dihydro-2H-pyran-2-one (7) was transformed into indolizidine 11 via a sequence of reactions involving methanolysis of the lactone ring, intramolecular alkylation of the nitrogen atom promoted by a carbontetrabromide-triphenylphosphine mixture and hydrogenolysis of the N single bond O bond. Decarboxylation of 11 provided known 7-hydroxylentiginosine derivative 14, whereas oxidative decarboxylation gave indolizidine 15 structurally related to castanospermine.