NMR-based metabolomics as a quality control tool for herbal products

The full potential of the herbal market is mainly not realised due to the lack of knowledge of the chemical composition of most herbal products. The growth potential of the herbal medicine industry can only be achieved if the composition of herbal medicine is standardised to ensure proper quality control and accountability. Plant-based nuclear magnetic resonance metabolomics is one such way of ensuring quick and reliable quality control and metabolite profiling to ensure quality and reproducibility of herbal medicine. Nuclear magnetic resonance-based metabolomics is robust and relatively easy to use, thus ensuring that herbal medicine can be verified and quality controlled much quicker and more accurate than is currently the case. Although nuclear magnetic resonance is not as sensitive as other analytical techniques such as liquid chromatography and gas chromatography–mass spectroscopy, it is far more reproducible, non-destructive, covers a much wider dynamic range and sample preparation is simpler and quicker to use. Economical development of herbal medicine and the use of nuclear magnetic resonance-based metabolomics should go hand in hand for a better future for herbal medicine. In this review an introduction is given to herbal extracts as therapeutic agents and to the quality control aspects of herbal medicine by means of metabolomics. The experimental methodology for plant metabolomics which covers extraction, nuclear magnetic resonance analysis and multivariate data analysis is also discussed. Some examples are given on the possible applications of nuclear magnetic resonance-based metabolomics in the industry and finally the future of nuclear magnetic resonance-based metabolomics is discussed regarding advances in research and development.http://www.elsevier.com/locate/sajbhb2016Plant Scienc

The influence of teacher feedback on children's perceptions of student–teacher relationships

Background Teachers can deliver feedback using person (‘you are clever’) or process terms (‘you worked hard’). Person feedback can lead to negative academic outcomes, but there is little experimental research examining the impact of feedback on children's perceptions of the student–teacher relationship. Aim We examined the effects of person, process, and no feedback on children's perceptions of their relationship with a (fictional) teacher following success and failure. Samples Participants were British children (145 aged 9–11 in experiment 1 and 98 aged 7–11 in experiment 2). Method In experiment 1, participants read three scenarios where they succeeded and received one of two types of praise (person or process) or no praise. Participants then read two scenarios where they failed. In experiment 2, participants read that they had failed in three tasks and received one of two types of criticism (person or process) or no criticism. Participants then read two scenarios where they succeeded. They rated how much they liked the teacher and how much they felt that the teacher liked them. Results Children felt more positive about the student–teacher relationship following success than failure. Type of praise did not influence perceptions of the student–teacher relationship following success or failure. However, person criticism led children to view the student–teacher relationship more negatively following failure and maintain this negative view following the first success. Conclusions Success appears to be important for developing positive student–teacher relationships. In response to failure, teachers could avoid person criticism which may negatively influence the student–teacher relationship

Identification of anti-HIV biomarkers of Helichrysum species by NMR-based metabolomic analysis

Several species of the Helichrysum genus have been used ethnobotanically to treat conditions that we today know have been caused by viral infections. Since HIV is a modern disease with no ethnobotanical history, we commenced with a study on the antiHIV activity of several Helichrysum species. Drug discovery of small molecules from natural resources that is based on the integration of chemical and biological activity by means of metabolomical analyses, enables faster and a more cost-effective path to identify active compounds without the need for a long process of bioassay-guided fractionation. This study used metabolomics to identify anti-HIV compounds as biomarkers from 57 Helichrysum species in a combined study of the chemical and biological data of two previous studies. In the OPLS-DA and hierarchical cluster analyses, anti-HIV activity data was included as a secondary observation, which assisted in the correlation of the phytochemical composition and biological activity of the samples. Clear grouping revealed similarity in chemical composition and bioactivity of the samples. Based on the biological activity of polar extracts, there was a distinct phytochemical difference between active and non-active groups of extracts. This NMR-based metabolomic investigation showed that the chlorogenic acids, compounds with cinnamoyl functional groups, and quinic acid were the most prominent compounds in the Helichrysum species with anti-HIV activity. This study further revealed that the chlorogenic acid type compounds and quinic acid are biomarkers for anti-HIV activity.The National Research Foundation of South Africa.https://www.frontiersin.org/journals/pharmacologydm2022Plant Production and Soil Scienc

State space exploration in Markov Models

Performance and dependability analysis is usually based on Markov models. One of the main problems faced by the analyst is the large state space cardinality of the Markov chain associated with the model, which precludes not only the model solution, but also the generation of the transition rate matrix. However, in many real system models, most of the probability mass is concentred in a small number of states in comparison with the whole state space. Therefore, performability measures may be accurately evaluated from these "high probable" states. In this paper, we present as algorithm to generate the most probable state the is more efficient than previous algorithms in the literature. We also address the problem of calculating measures of interest and show how bounds on some measures can b efficiently calculated.Análise de desempenho e dependabilidade baseia-se usualmente em modelos Markovianos. Um dos principais problemas que o analista encontra é a grande cardinalidade do espaço de estados da cadeias de Markov associada ao modelo, o que impede não somente a solução do modelo, mas também a geração da matriz de transição de estados. Entretanto, em muitos modelos de sistemas reais, a maioria da massa de probabilidade está concentrada em um pequeno número de estados em comparação com a totalidade do espaço dos estados. Por conseguinte, medidas de desempenhabilidade ('performability') podem ser avaliadas com precisão a partir desses estados mais prováveis. Neste artigo, apresentamos um algoritmo de geração dos estados mais prováveis que é mais eficiente que algoritmos anteriormente propostos na literatura. Abordaremos também o problema de cálculo das medidas de interesse e mostraremos como limites para algumas medidas podem ser eficientemente calculados

Paediatric obsessive-compulsive disorder and depressive symptoms: clinical correlates and CBT treatment outcomes.

Depression frequently co-occurs with paediatric obsessive-compulsive disorder (OCD), yet the clinical correlates and impact of depression on CBT outcomes remain unclear. The prevalence and clinical correlates of depression were examined in a paediatric specialist OCD-clinic sample (N = 295; Mean = 15 [7 - 18] years, 42 % female), using both dimensional (Beck Depression Inventory-youth; n = 261) and diagnostic (Development and Wellbeing Assessment; n = 127) measures of depression. The impact of depressive symptoms and suspected disorders on post-treatment OCD severity was examined in a sub-sample who received CBT, with or without SSRI medication (N = 100). Fifty-one per-cent of patients reported moderately or extremely elevated depressive symptoms and 26 % (95 % CI: 18 - 34) met criteria for a suspected depressive disorder. Depressive symptoms and depressive disorders were associated with worse OCD symptom severity and global functioning prior to CBT. Individuals with depression were more likely to be female, have had a psychiatric inpatient admission and less likely to be attending school (ps < 0.01). OCD and depressive symptom severity significantly decreased after CBT. Depressive symptoms and depressive disorders predicted worse post-treatment OCD severity (βs = 0.19 and 0.26, ps < 0.05) but became non-significant when controlling for pre-treatment OCD severity (βs = 0.05 and 0.13, ns). Depression is common in paediatric OCD and is associated with more severe OCD and poorer functioning. However, depression severity decreases over the course of CBT for OCD and is not independently associated with worse outcomes, supporting the recommendation for treatment as usual in the presence of depressive symptoms

Forest Cover Classification by Optimal Segmentation of High Resolution Satellite Imagery

This study investigated whether high-resolution satellite imagery is suitable for preparing a detailed digital forest cover map that discriminates forest cover at the tree species level. First, we tried to find an optimal process for segmenting the high-resolution images using a region-growing method with the scale, color and shape factors in Definiens® Professional 5.0. The image was classified by a traditional, pixel-based, maximum likelihood classification approach using the spectral information of the pixels. The pixels in each segment were reclassified using a segment-based classification (SBC) with a majority rule. Segmentation with strongly weighted color was less sensitive to the scale parameter and led to optimal forest cover segmentation and classification. The pixel-based classification (PBC) suffered from the “salt-and-pepper effect” and performed poorly in the classification of forest cover types, whereas the SBC helped to attenuate the effect and notably improved the classification accuracy. As a whole, SBC proved to be more suitable for classifying and delineating forest cover using high-resolution satellite images

Behavioral, Physiologic, and Habitat Influences on the Dynamics of Puumala virus Infection in Bank Voles (Clethrionomys glareolus)

Populations of bank voles (Clethrionomys glareolus) were monitored during a 4-year study in southern Belgium to assess the influence of agonistic behavior, reproductive status, mobility, and distribution of the rodents on the dynamics of Puumala virus (abbreviation: PUUV; genus: Hantavirus) infection. Concordance was high between data from serologic testing and results of viral RNA detection. Wounds resulting from biting or scratching were observed mainly in adult rodents. Hantavirus infection in adults was associated with wounds in the fall, i.e., at the end of the breeding season, but not in spring. In addition, sexually active animals were significantly more often wounded and positive for infection. Hantavirus infection was associated with higher mobility in juvenile and subadult males. Seroconversions observed 6 months apart also occurred more frequently in animals that had moved longer distances from their original capture point. During nonepidemic years, the distribution of infection was patchy, and positive foci were mainly located in dense ground vegetation

Systemic immune dysregulation in early breast cancer is associated with decreased plasma levels of both soluble co-inhibitory and co-stimulatory immune checkpoint molecules

Breast cancer cells exploit the up-regulation or down-regulation of immune checkpoint proteins to evade anti-tumor immune responses. To explore the possible involvement of this mechanism in promoting systemic immunosuppression, the pre-treatment levels of soluble co-inhibitory and co-stimulatory immune checkpoint molecules, as well as those of cytokines, chemokines, and growth factors were measured in 98 newly diagnosed breast cancer patients and compared with those of 45 healthy controls using multiplex bead array and ELISA technologies. Plasma concentrations of the co-stimulatory immune checkpoints, GITR, GITRL, CD27, CD28, CD40, CD80, CD86 and ICOS, as well as the co-inhibitory molecules, PD-L1, CTLA-4 and TIM-3, were all significantly lower in early breast cancer patients compared to healthy controls, as were those of HVEM and sTLR-2, whereas the plasma concentrations of CX3CL1 (fractalkine), CCL5 (RANTES) and those of the growth factors, M-CSF, FGF-21 and GDF-15 were significantly increased. However, when analyzed according to the patients’ breast cancer characteristics, these being triple negative breast cancer (TNBC) vs. non-TNBC, tumor size, stage, nodal status and age, no significant differences were detected between the plasma levels of the various immune checkpoint molecules, cytokines, chemokines and growth factors. Additionally, none of these biomarkers correlated with pathological complete response. This study has identified low plasma levels of soluble co-stimulatory and co-inhibitory immune checkpoint molecules in newly diagnosed, non-metastatic breast cancer patients compared to healthy controls, which is a novel finding seemingly consistent with a state of systemic immune dysregulation. Plausible mechanisms include an association with elevated levels of M-CSF and CCL5, implicating the involvement of immune suppressor cells of the M2-macrophage/monocyte phenotype as possible drivers of this state of systemic immune quiescence/dysregulation.The Cancer Association of South Africa (CANSA).https://www.frontiersin.org/journals/immunologydm2022Immunolog

Dysregulation of systemic soluble immune checkpoints in early breast cancer is attenuated following administration of neoadjuvant chemotherapy and is associated with recovery of CD27, CD28, CD40, CD80, ICOS and GITR and substantially increased levels of PD-L1, LAG-3 and TIM-3

DATA AVAILABILITY STATEMENT : The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.SUPPLEMETARY MATERIAL : SUPPLEMENTARY FIGURE 1 Box and whisker plots depicting the progressive changes in the median plasma concentrations (with 95% confidence limits) of three co-inhibitory immune checkpoints (BTLA, CTLA-4 and PD-1) throughout the course of neoadjuvant chemotherapy (NAC) (pre-treatment/diagnosis, post-NAC and post-surgery) in relation to the corresponding median values of the control subjects. The p values represent the comparison between pre-treatment/ diagnosis and post-NAC values.SUPPLEMENTARY FIGURE 2 Box and whisker plots depicting the progressive changes in the median plasma concentrations (with 95% confidence limits) of the remaining four co-stimulatory immune checkpoints (CD28, CD40, CD86 and GITRL) throughout the course of neoadjuvant chemotherapy (NAC) (pretreatment/ diagnosis, post-NAC and post-surgery) in relation to the corresponding median values of the control subjects. The p values represent the comparison between the pre-treatment/diagnosis and post- NAC values.SUPPLEMENTARY FIGURE 3 Box and whisker plots depicting the progressive changes in the median plasma concentrations (with 95% confidence limits) of the two dual-activity immune checkpoints (TLR-2 and HVEM) throughout the course of neoadjuvant chemotherapy (NAC) (pre-treatment/diagnosis, post-NAC and post-surgery) in relation to the corresponding median values of the control subjects. The p values represent the comparison between the pre-treatment/ diagnosis and post-NAC values.SUPPLEMENTARY FIGURE 4 Histological photomicrographs of pre-treatment tissue of a patient who attained a pathological complete response. (A) x20 Magnification: Core biopsy hematoxylin and eosin (H&E) stained slide breast carcinoma no special type (NST), prior to therapy. (B) X10 Magnification: Positive ECadherin immunoperoxidase stain of tumor confirming ductal differentiation. (C) x20 Magnification: Estrogen receptor immunoperoxidase stain of tumor, showing no staining (ER negative).SUPPLEMENTARY FIGURE 5 Histological photomicrographs of pre-treatment tissue of a patient who attained a pathological complete response. (A) x20 Magnification: Progesterone receptor immunoperoxidase stain of tumor (PR negative). (B) x20 Magnification: HER2 immunoperoxidase stain of tumor (HER2 negative). (C) x20 Magnification :Ki67 immunoperoxidase stain of tumor (90% of tumor cells staining positive).SUPPLEMENTARY FIGURE 6 Histological photomicrographs of post-surgery tissue obtained during surgery of a patient who attained a pathological complete response. (A) X10 Magnification: Tumor bed post chemotherapy showing stromal fibrosis and dystrophic calcification with NO tumor cells H&E. (B) X10 Magnification: Tumor bed post chemotherapy showing loose fibrovascular response and elastosis with NO tumor cells H&E. (C) x20 Magnification: MNF116 (broad pancytokeratin) immunoperoxidase stain of tumor bed post chemotherapy showing NO residual staining tumor cells.Neoadjuvant chemotherapy (NAC) may alter the immune landscape of patients with early breast cancer (BC), potentially setting the scene for more effective implementation of checkpoint-targeted immunotherapy. This issue has been investigated in the current study in which alterations in the plasma concentrations of 16 soluble co-stimulatory and co-inhibitory, immune checkpoints were measured sequentially in a cohort of newly diagnosed, early BC patients (n=72), pre-treatment, post-NAC and post-surgery using a Multiplex® bead array platform. Relative to a group of healthy control subjects (n=45), the median pre-treatment levels of five co-stimulatory (CD27, CD40, GITRL, ICOS, GITR) and three co-inhibitory (TIM-3, CTLA-4, PD-L1) soluble checkpoints were significantly lower in the BC patients vs. controls (p<0.021-p<0.0001; and p<0.008-p<0.00001, respectively). Following NAC, the plasma levels of six soluble co-stimulatory checkpoints (CD28, CD40, ICOS, CD27, CD80, GITR), all involved in activation of CD8+ cytotoxic T cells, were significantly increased (p<0.04-p<0.00001), comparable with control values and remained at these levels post-surgery. Of the soluble co-inhibitory checkpoints, three (LAG-3, PDL1, TIM-3) increased significantly post-NAC, reaching levels significantly greater than those of the control group. PD-1 remained unchanged, while BTLA and CTLA-4 decreased significantly (p<0.03 and p<0.00001, respectively). Normalization of soluble co-stimulatory immune checkpoints is seemingly indicative of reversal of systemic immune dysregulation following administration of NAC in early BC, while recovery of immune homeostasis may explain the increased levels of several negative checkpoint proteins, albeit with the exceptions of CTLA-4 and PD-1. Although a pathological complete response (pCR) was documented in 61% of patients (mostly triple-negative BC), surprisingly, none of the soluble immune checkpoints correlated with the pCR, either pre-treatment or post-NAC. Nevertheless, in the case of the co-stimulatory ICMs, these novel findings are indicative of the immune-restorative potential of NAC in early BC, while in the case of the co-inhibitory ICMs, elevated levels of soluble PD-L1, LAG-3 and TIM-3 post-NAC underscore the augmentative immunotherapeutic promise of targeting these molecules, either individually or in combination, as a strategy, which may contribute to the improved management of early BC.The Cancer Association of South Africa (CANSA).http://www.frontiersin.org/Oncologyam2024ImmunologySDG-03:Good heatlh and well-bein