Genomic diversity and antimicrobial resistance in clinical Klebsiella pneumoniae isolates from tertiary hospitals in Southern Ghana.

OBJECTIVES: Comprehensive data on the genomic epidemiology of hospital-associated Klebsiella pneumoniae in Ghana are scarce. This study investigated the genomic diversity, antimicrobial resistance patterns, and clonal relationships of 103 clinical K. pneumoniae isolates from five tertiary hospitals in Southern Ghana-predominantly from paediatric patients aged under 5 years (67/103; 65%), with the majority collected from urine (32/103; 31%) and blood (25/103; 24%) cultures. METHODS: We generated hybrid Nanopore-Illumina assemblies and employed Pathogenwatch for genotyping via Kaptive [capsular (K) locus and lipopolysaccharide (O) antigens] and Kleborate (antimicrobial resistance and hypervirulence) and determined clonal relationships using core-genome MLST (cgMLST). RESULTS: Of 44 distinct STs detected, ST133 was the most common, comprising 23% of isolates (n = 23/103). KL116 (28/103; 27%) and O1 (66/103; 64%) were the most prevalent K-locus and O-antigen types. Single-linkage clustering highlighted the global spread of MDR clones such as ST15, ST307, ST17, ST11, ST101 and ST48, with minimal allele differences (1-5) from publicly available genomes worldwide. Conversely, 17 isolates constituted novel clonal groups and lacked close relatives among publicly available genomes, displaying unique genetic diversity within our study population. A significant proportion of isolates (88/103; 85%) carried resistance genes for ≥3 antibiotic classes, with the blaCTX-M-15 gene present in 78% (n = 80/103). Carbapenem resistance, predominantly due to blaOXA-181 and blaNDM-1 genes, was found in 10% (n = 10/103) of the isolates. CONCLUSIONS: Our findings reveal a complex genomic landscape of K. pneumoniae in Southern Ghana, underscoring the critical need for ongoing genomic surveillance to manage the substantial burden of antimicrobial resistance.

Predicting factors influencing perceived online learning experience among primary students utilizing structural equation modeling Forest Classifier approach.

Introduction: Amid the COVID-19 pandemic, the temporary closure of educational institutions led to the adoption of remote or online learning delivery. Challenges, especially for grade schools were evident. Objective: This study aimed to identify factors affecting the perceived online discussion experience of Filipino primary students through distance learning in the National Capital Region, Philippines. Method: Variables such as cognitive presence, teaching presence, social presence, and online discussion experience were investigated simultaneously by utilizing the structural equation modeling (SEM) and random forest classifier (RFC) approach. A total of 385 currently enrolled Filipino grade school student participants were surveyed. Results: Results show that cognitive presence has the most significant impact on the perceived online discussion experience, followed by teaching presence, and social presence. This study is the first study that analyzed the online discussion experience among grade school students in online education in the Philippines considering SEM and RFC. It was seen that highly significant factors such as teaching presence, cognitive presence, social presence, triggering events, and exploration will lead to high and very high learning experience with grade school students. Conclusion: The findings of this study would be significant for teachers, educational institutions, and government agencies to improve the online delivery of primary education in the country. In addition, this study presents a reliable model and results which can be extended and applied for academicians, educational institutions, and the education sector to develop ways in enhancing the online delivery of primary education worldwide.

Introduction: Au milieu de la pandémie de COVID-19, la fermeture temporaire des établissements d'enseignement a conduit à l'adoption de la prestation d'apprentissage à distance ou en ligne. Les défis, en particulier pour les écoles primaires, étaient évidents. Objectif: Cette étude visait à identifier les facteurs affectant l'expérience de discussion en ligne perçue des élèves philippins du primaire par le biais de l'apprentissage à distance dans la région de la capitale nationale, aux Philippines. Méthode: Des variables telles que la présence cognitive, la présence dans l'enseignement, la présence sociale et l'expérience de discussion en ligne ont été étudiées simultanément en utilisant l'approche de structural equation modeling (SEM) et de Random Forest classifier (RFC). Un total de 385 élèves philippins actuellement inscrits à l'école primaire ont été interrogés. Résultats: Les résultats montrent que la présence cognitive a l'impact le plus significatif sur l'expérience de discussion en ligne perçue, suivie de la présence pédagogique et de la présence sociale. Cette étude est la première étude qui a analysé l'expérience de discussion en ligne parmi les élèves du primaire dans l'éducation en ligne aux Philippines en tenant compte du SEM et du RFC. Il a été constaté que des facteurs très importants tels que la présence d'enseignement, la présence cognitive, la présence sociale, les événements déclencheurs et l'exploration conduiront à une expérience d'apprentissage élevée et très élevée avec les élèves du primaire. Conclusion: En outre, cette étude présente un modèle et des résultats fiables qui peuvent être étendus et appliqués aux universitaires, aux établissements d'enseignement et au secteur de l'éducation afin de développer des moyens d'améliorer la prestation en ligne de l'enseignement primaire dans le monde entier.

Chemotherapy negatively impacts the tumor immune microenvironment in NSCLC: an analysis of pre- and post-treatment biopsies in the multi-center SAKK19/09 study.

BACKGROUND: Over the past few years, immune checkpoint inhibitors have changed the therapeutic landscape of non-small-cell lung cancer (NSCLC). Response to immune checkpoint inhibitors correlates with a pre-existing anti-tumoral immune response. Checkpoint inhibitors have been introduced as second-line therapy and are only very recently used as monotherapy or in combination with chemotherapy as first-line treatment of NSCLC. However, the effect of conventional first-line platinum-based chemotherapy on the immune infiltrate in the tumor is largely unknown. METHODS: We measured the gene expression of a custom set of 201 cancer- and immune-related genes in 100 NSCLC tumor biopsies collected before chemotherapy and 33 re-biopsies after platinum-based chemotherapy at the time point of progression. For 29 patients matched pre- and post-chemotherapy samples could be evaluated. RESULTS: We identified a cluster of 47 co-expressed immune genes, including PDCD1 (PD1) and CD274 (PD-L1), along with three other co-expression clusters. Chemotherapy decreased the average gene expression of the immune cluster while no effect was observed on the other three cluster. Within this immune cluster, CTLA4, LAG3, TNFRSF18, CD80 and FOXP3 were found to be significantly decreased in patient-matched samples after chemotherapy. CONCLUSION: Our results suggest that conventional platinum-based chemotherapy negatively impacts the immune microenvironment at the time point of secondary progression.

Exploitation of a novel phenothiazine derivative for its anti-cancer activities in malignant glioblastoma.

Glioblastoma remains the most malignant of all primary adult brain tumours with poor patient survival and limited treatment options. This study adopts a drug repurposing approach by investigating the anti-cancer activity of a derivative of the antipsychotic drug phenothiazine (DS00329) in malignant U251 and U87 glioblastoma cells. Results from MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and clonogenic assays showed that DS00329 inhibited short-term glioblastoma cell viability and long-term survival while sparing non-cancerous cells. Western blot analysis with an antibody to γH2AX showed that DS00329 induced DNA damage and flow cytometry and western blotting confirmed that it triggered a G1 cell cycle arrest which correlated with decreased levels in Cyclin A, Cyclin B, Cyclin D1 and cyclin dependent kinase 2 and an increase in levels of the cyclin dependent kinase inhibitor p21. DS00329 treated glioblastoma cells exhibited morphological and molecular markers typical of apoptotic cells such as membrane blebbing and cell shrinkage and an increase in levels of cleaved PARP. Flow cytometry with annexin V-FITC/propidium iodide staining confirmed that DS00329 induced apoptotic cell death in glioblastoma cells. We also show that DS00329 treatment of glioblastoma cells led to an increase in the autophagosome marker LC3-II and autophagy inhibition studies using bafilomycin A1 and wortmannin, showed that DS00329-induced-autophagy was a pro-death mechanism. Furthermore, DS00329 treatment of glioblastoma cells inhibited the phosphatidylinositol 3'-kinase/Akt cell survival pathway. Our findings suggest that DS00329 may be an effective treatment for glioblastoma and provide a rationale for further exploration and validation of the use of phenothiazines and their derivatives in the treatment of glioblastoma.

The functionality of African-specific variants in the TGFB1 regulatory region and their potential role in HIVAN.

BACKGROUND: Transcription of transforming growth factor beta-1 (TGF-ß1) is regulated by a polymorphic promoter region containing African-specific single nucleotide polymorphisms (SNPs). Some of these SNPs have higher frequencies among Southern Africans compared to other African populations and their functionality has only been partially studied. Due to the high prevalence of HIV-associated nephropathy (HIVAN) in Africans we hypothesized that functional African TGFB1-promoter SNPs may contribute to HIVAN pathogenesis. METHODS: The functionality of the TGFB1 -1347 C>T variant and African-specific variants (-1287 G>A, -1154 C>T, -387 C>T and -14 G>A) were examined by measuring reporter gene expression in kidney and fibroblast cell lines co-transfected with TGFB1-promoter constructs and an HIV-Tat expression vector. TGF-ß1 immunohistochemical staining was performed on kidney biopsies with HIVAN (n = 18) and compared to control biopsies without HIVAN or tubulointerstitial disease (n = 12) using semi-quantitative and digital image analysis. HIVAN cases were genotyped for TGFB1 -1347 and -387 SNP variants. RESULTS: TGFB1-promoter haplotypes containing the African -387 T-allele resulted in ~ five-fold repression of TGFB1-promoter activity compared to -387 C haplotypes (p ≤ 0.024). HIV-Tat upregulated TGFB1-promoter activity for haplotypes containing -1347 T and -387 T in transfected renal cells (≈ 1.6-fold; p ≤ 0.030) and fibroblasts (≈ 1.3-fold; p ≤ 0.016). The renal interstitium from HIVAN biopsies, compared to HIV-positive and -negative controls, differed in the semi-quantitative TGF-ß1 staining and digital optical density analyses. The TGFB1 -1347 and -387 genotypes in HIVAN cases were similar to population controls. CONCLUSION: African-specific haplotypes lower TGFB1-promoter activity and expression levels and HIV-Tat upregulates TGFB1 promoter activity irrespective of the haplotype.

Performances of two different panfungal PCRs to detect mould DNA in formalin-fixed paraffin-embedded tissue: what are the limiting factors?

BACKGROUND: Detection of fungal DNA from formalin-fixed, paraffin-embedded (FFPE) tissue is challenging due to degradation of DNA and presence of PCR inhibitors in these samples. We analyzed FFPE samples of 26 patients by panfungal PCR and compared the results to the composite diagnosis according to the European Organization for Research and Treatment of Cancer (EORTC) criteria. Additionally we analyzed the quality of human and fungal DNA and their level of age-dependent degradation, as well as the existence of PCR inhibition in these tissue samples. METHODS: We evaluated two 45-cycle panfungal PCR tests that target the internal transcribed spacer 2 (ITS2) as well as the ITS1-5.8S-ITS2 (ITS1-2) region. The PCRs were applied to 27 FFPE specimens from 26 patients with proven invasive fungal disease (IFD), and one patient with culture and histologically negative but PCR-positive fungal infection collected at our institution from 2003 to 2010. Quality of DNA in FFPE tissue samples was evaluated using fragments of the beta-globin gene for multiplex PCR, inhibition of PCR amplification was evaluated by spiking of C. krusei DNA to each PCR premix. RESULTS: In 27 FFPE samples the ITS2 PCR targeting the shorter fragment showed a higher detection rate with a sensitivity of 53.8% compared to the ITS1-2 fragment (sensitivity 38%). Significant time-dependent degradation of human DNA in FFPE sample extracts was detected based on partial beta-globin gene amplification which was not in correlation to successful panfungal PCR identification of fungal organisms. The analytical sensitivity of both assays compared with culture was 60 CFU/ml of a Candida krusei reference strain. The performance of the two tests in an Aspergillus proficiency panel of an international external quality assessment programme showed considerable sensitivity. CONCLUSION: Panfungal diagnostic PCR assays applied on FFPE specimens provide accurate identification of molds in highly degraded tissue samples and correct identification in samples stored up to 7 years despite sensitivity limitations, mainly caused by partial PCR inhibition and DNA degradation by formalin.

Principal component and cluster analysis of layer V pyramidal cells in visual and non-visual cortical areas projecting to the primary visual cortex of the mouse.

The long-distance corticocortical connections between visual and nonvisual sensory areas that arise from pyramidal neurons located within layer V can be considered as a subpopulation of feedback connections. The purpose of the present study is to determine if layer V pyramidal neurons from visual and nonvisual sensory cortical areas that project onto the visual cortex (V1) constitute a homogeneous population of cells. Additionally, we ask whether dendritic arborization relates to the target, the sensory modality, the hierarchical level, or laterality of the source cortical area. Complete 3D reconstructions of dendritic arbors of retrogradely labeled layer V pyramidal neurons were performed for neurons of the primary auditory (A1) and somatosensory (S1) cortices and from the lateral (V2L) and medial (V2M) parts of the secondary visual cortices of both hemispheres. The morphological parameters extracted from these reconstructions were subjected to principal component analysis (PCA) and cluster analysis. The PCA showed that neurons are distributed within a continuous range of morphologies and do not form discrete groups. Nevertheless, the cluster analysis defines neuronal groups that share similar features. Each cortical area includes neurons belonging to several clusters. We suggest that layer V feedback connections within a single cortical area comprise several cell types.

Nurses and Voluntary Assisted Dying: How the Australian Capital Territory's Law Could Change the Australian Regulatory Landscape.

On June 5, 2024, the Australian Capital Territory passed a law to permit voluntary assisted dying ("VAD"). The Australian Capital Territory became the first Australian jurisdiction to permit nurse practitioners to assess eligibility for VAD. Given evidence of access barriers to VAD in Australia, including difficulty finding a doctor willing to assist, the Australian Capital Territory's approach should prompt consideration of whether the role of nurses in VAD should be expanded in other Australian jurisdictions. Drawing on lessons from Canada, which currently permits nurse practitioners to assess patient eligibility, we argue that the time has come for Australian jurisdictions to expand the role of nurses in VAD systems. This would be an important step in ensuring access to VAD for patients in practice. Attention, however, must also be paid to ensuring adequate remuneration of nurses (and doctors) if this goal of promoting access is to be achieved in practice.

Binuclear palladacycles with ionisable and non-ionisable tethers as anticancer agents.

The search for novel anticancer agents to replace the current platinum-based treatments remains an ongoing process. Palladacycles have shown excellent promise as demonstrated by our previous work which yielded BTC2, a binuclear palladadycle with a non-ionisable polyethylene glycol (PEG) tether. Here, we explore the importance of the PEG-tether length on the anticancer activity of the binuclear palladacycles by comparing three analogous binuclear palladacycles, BTC2, BTC5 and BTC6, in the oestrogen receptor positive MCF7 and triple-negative MDA-MB-231 breast cancer cell lines. In addition, these are compared to another analogue with an ionisable morpholine tether, BTC7. Potent anticancer activity was revealed through cell viability studies (MTT assays) revealed that while BTC6 showed similar potent anticancer activity as BTC2, it was less toxic towards non-cancerous cell lines. Interestingly, BTC7 and BTCF were less potent than the PEGylated palladacycles but showed significantly improved selectivity towards the triple-negative breast cancer cells. Cell death analysis showed that BTC7 and BTCF significantly induced apoptosis in both the cancer cell lines while the PEGylated complexes induced both apoptosis and secondary necrosis. Furthermore, experimental and computational DNA binding studies indicated partial intercalation and groove binding as the modes of action for the PEGylated palladacycles. Similarly, experimental and computational BSA binding studies indicated and specific binding sites in BSA dependent on the nature of the tethers on the complexes.

Reproducibility of linear and angular cephalometric measurements obtained by an artificial-intelligence assisted software (WebCeph) in comparison with digital software (AutoCEPH) and manual tracing method.

INTRODUCTION: It has been suggested that human errors during manual tracing of linear/angular cephalometric parameters can be eliminated by using computer-aided analysis. The landmarks, however, are located manually and the computer system completes the analysis. With the advent of Artificial Intelligence in the field of Dentistry, automatic location of the landmarks has become a promising tool in digital Orthodontics. METHODS: Fifty pretreatment lateral cephalograms obtained from the Orthodontic department of SRM dental college (India) were used. Analysis were done by the same investigator using the following methods: WebCeph™, AutoCEPH© for Windows or manual tracing. Landmark identification was carried out automatically by Artificial Intelligence in WebCeph™ and with a mouse driven cursor in AutoCEPH©, and manually using acetate sheet and 0.3-mm pencil, ruler and a protractor. The mean differences of the cephalometric parameters obtained between the three methods were calculated using ANOVA with statistical significance set at p<0.05. Intraclass correlation coefficient (ICC) was used to determine both reproducibility and agreement between linear and angular measurements obtained from the three methods and intrarater reliability of repeated measurements. ICC value of >0.75 indicated good agreement. RESULTS: Intraclass correlation coefficient between the three groups was >0.830, showing good level of agreement, and the value within each group was >0.950, indicating high intrarater reliability. CONCLUSION: Artificial Intelligence assisted software showed good agreement with AutoCEPH© and manual tracing for all the cephalometric measurements.

Dactylogyrus spp. (Dactylogyridae, Monogenea) from tinfoil barb, Barbonymus schwanenfeldii imported into South Africa: morphometric and molecular characterisation.

This study reports on three species of Dactylogyrus Diesing, 1850 (Dactylogyridae) collected from tinfoil barb, Barbonymus schwanenfeldii (Bleeker) which were imported into South Africa as ornamental fish from Sri Lanka and Thailand. Supplementary morphometric characterisation and molecular data (partial 18S and 28S rDNA, and ITS1 region sequences) are presented for Dactylogyrus lampam (Lim & Furtado, 1986), Dactylogyrus tapienensis Chinabut & Lim, 1993 and Dactylogyrus viticulus Chinabut & Lim, 1993. Prevalence of Dactylogyrus spp. infection was 87% and 80% for fish from Sri Lanka and Thailand, respectively. Composition of the parasites between the fish of each origin differed. All three species were found to infect fish from Thailand, but only D. lampam was present on the fish received from Sri Lanka. Phylogenetic analysis revealed the position of studied species, with D. lampam clustering within the lineages of varicorhini-type species, while D. tapienensis and D. viticulus form a sister lineage to Dactylogyrus spp. associated with Cyprinus carpio L. and Carassius spp., species parasitising central African large cyprinids (Labeo Cuvier), and species parasitising African and Middle Eastern Carasobarbus spp.

Title: Dactylogyrus spp. (Dactylogyridae, Monogenea) de Barbonymus schwanenfeldii importé en Afrique du Sud : caractérisation morphométrique et moléculaire. Abstract: Cette étude porte sur trois espèces de Dactylogyrus Diesing, 1850 (Dactylogyridae), prélevées sur des Barbonymus schwanenfeldii (Bleeker) qui ont été importés en Afrique du Sud comme poissons d'ornement depuis le Sri Lanka et la Thaïlande. Une caractérisation morphométrique et des données moléculaires supplémentaires (ADNr 18S et 28S partiels et séquences de la région ITS1) sont présentées pour Dactylogyrus lampam (Lim & Furtado, 1986), Dactylogyrus tapienensis Chinabut & Lim, 1993 et Dactylogyrus viticulus Chinabut & Lim, 1993. La prévalence de l'infection par les Dactylogyrus spp. était respectivement de 87 % et 80 % pour les poissons du Sri Lanka et de Thaïlande. La composition des parasites entre les poissons des deux origines différait. Les trois espèces infectaient les poissons de Thaïlande, mais seul D. lampam était présent sur les poissons du Sri Lanka. L'analyse phylogénétique a révélé la position des espèces étudiées, D. lampam se regroupant dans les lignées d'espèces de type varicorhini, tandis que D. tapienensis et D. viticulus forment une lignée sœur des Dactylogyrus spp. associés à Cyprinus carpio L. et Carassius spp., espèces parasitant les grands cyprinidés d'Afrique centrale (Labeo Cuvier), et espèces parasitant les Carasobarbus spp. d'Afrique et du Moyen-Orient.

Neoadjuvant treatment does not influence PD-L1 expression in stage III non-small-cell lung cancer: a retrospective analysis of tumor samples from the trials SAKK 16/96, 16/00, 16/01, and 16/14.

BACKGROUND: The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-PD-L1 axis. Little is known about the impact of neoadjuvant treatment on PD-L1 expression. PATIENTS AND METHODS: We assessed PD-L1 expression by immunohistochemistry (Ventana SP263 assay) on tumor cells in treatment-naive diagnostic tumor samples and matched lung resections from patients with stage III non-small-cell lung cancer included in the Swiss Group for Clinical Cancer Research (SAKK) trials 16/96, 16/00, 16/01, and 16/14. All patients received neoadjuvant chemotherapy (CT) with cisplatin/docetaxel, either as single modality (CT), with sequential radiotherapy [chemoradiation therapy (CRT)] or with the PD-L1 inhibitor durvalumab (CT + ICI). RESULTS: Overall, 132 paired tumor samples were analyzed from patients with neoadjuvant CT (n = 69), CRT (n = 33) and CT + ICI (n = 30). For CT and CRT, PD-L1 expression before and after neoadjuvant treatment did not differ significantly (Wilcoxon test, P = 0.94). Likewise, no statistically significant difference was observed between CT and CRT for PD-L1 expression after neoadjuvant treatment (P = 0.97). For CT + ICI, PD-L1 expression before and after neoadjuvant treatment also did not differ significantly (Wilcoxon test, P > 0.99). Event-free survival and overall survival for patients with downregulation or upregulation of PD-L1 expression after neoadjuvant treatment were similar. CONCLUSIONS: In our cohort of patients neoadjuvant treatment did not influence PD-L1 expression, irrespective of the specific neoadjuvant treatment protocol. Dynamic change of PD-L1 expression did not correlate with event-free survival or overall survival.

Hydrogeochemical study of shallow carbonate aquifers, Rameswaram Island, India.

Groundwater quality assessment has been carried out based on physicochemical parameters (pH, EC, TDS, CO(3), HCO(3), Cl, SO(4), PO(4), NO(2), Ca(+2), Mg(+2), Na(+) and K(+)) and metal concentration in the Rameswaram Island from 25 bore wells. The Langelier Saturation Index of the groundwater shows positive values (63% samples) with a tendency to deposit the CaCO(3) in the majority of water samples. Scatter plot (Ca + Mg/HCO(3)) suggests carbonate weathering process, which is the main contributor of Ca(2+), Mg(2+) and HCO(3) ions to the water. Gibbs diagram suggests rock-water interaction dominance and evaporation dominance which are responsible for the change in the quality of water in the study area. NaCl and mixed CaNaHCO(3) facies are two main hydrogeochemical facies of groundwater. Mathematical calculations and graphical plots of geochemical data reveal that the groundwater of Rameswaram Island is influenced by natural weathering of rocks, anthropogenic activities and seawater intrusion due to over exploitation. Weathering and dissolution of carbonate and gypsum minerals also control the concentration of major ions (Ca(+2), Mg(+2), Na(+) and K(+)) in the groundwater. The nutrient concentration of groundwater is controlled to a large extent by the fertilizers used in agricultural lands and aquaforms. Comparison of geochemical data shows that majority of the groundwater samples are suitable for drinking water and irrigation purposes.

Valencene post-treatment exhibits cardioprotection via inhibiting cardiac hypertrophy, oxidative stress, nuclear factor- κB inflammatory pathway, and myocardial infarct size in isoproterenol-induced myocardial infarcted rats; A molecular study.

The growing burden of myocardial infarction (MI) becomes a major global health issue that is accountable for considerable mortality worldwide. Hence, it is obligatory to develop a new treatment for MI having lesser side effects. Cardiac hypertrophy, oxidative stress, and inflammatory pathways play crucial roles in the pathogenesis of MI. This investigation established the anti-cardiac hypertrophic, antioxidant, anti-inflammatory, and myocardial infarct size limiting effects of valencene. Rats were induced MI by isoproterenol (100 mg/kg body weight) and then treated with valencene and cardiac sensitive markers, cardiac hypertrophy, oxidative stress, markers of inflammation, nuclear factor- κB inflammatory pathway, and myocardial infarct size was estimated/determined. The serum cardiac diagnostic markers, cardiac hypertrophy, conjugated dienes, markers of inflammation, pro-inflammatory cytokines, and myocardial infarct size were significantly (P < 0.05) increased by isoproterenol. Further, antioxidant enzymes and anti-inflammatory cytokine gene were significantly (P < 0.05) decreased in the heart. The 2, 3, 5-triphenyl tetrazolium chloride dye staining revealed a larger infarct size. Moreover, histological results of myocardial infarcted rat's cardiac tissue revealed separation of cardiac muscle fibers, necrosis, and inflammatory cells. Post-treatment with valencene (12 mg/kg body weight) orally, daily, for two weeks to isoproterenol-induced myocardial infarcted rats reversed all above said structural, biochemical, molecular, and histological parameters investigated, by its anti-cardiac hypertrophic, antioxidant, anti-inflammatory, and myocardial infarct size limiting effects. Thus, valencene is a potential candidate for inhibiting cardiac hypertrophy, oxidative stress, nuclear factor- κB inflammatory pathway, and myocardial infarct size and exhibited cardioprotection in MI.

COVID-19 pandemic - Inequities and inequalities to exercise and their consequences on the physical and mental health of women with cardiovascular disease: recommendations on how to address the needs of women.

The coronavirus disease (COVID-19) pandemic disproportionately affects those with pre-existing conditions and has exacerbated gender inequalities. Cardiovascular disease (CVD) is the leading cause of death among Canadian women. Exercise improves physical and mental health and CVD management. Amid the pandemic, women are experiencing an increase in caregiving responsibilities, job insecurities, and domestic violence creating competing demands for prioritizing their health. Recommendations on how to meet the unique needs of Canadian women with CVD through exercise are provided. Novelty: Exercise recommendations amid the pandemic for women with CVD need to be flexible, feasible, and fun.

A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis.

Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198C>G SNP (odds ratio=8.6; P=0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5'-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198C>G SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression.

Secretory component of epithelial cells is a surface receptor for polymeric immunoglobulins.

Epithelial cells of human fetal intestines and of a colonic carcinoma cell line (HT-29) exhibited intracellular and surface binding of polymeric immunoglobulins of IgA and IgM classes; monomeric IgA and IgG did not bind to these cells. Secretory component was identified as the receptor involved in the immunoglobulin binding. This conclusion was confirmed by the following experiments: trypsin abrogated the surface binding of polymeric immunoglobulin, reappearance of surface secretory component (SC) restored immunoglobulin binding; the appearance of SC in developing fetal tissues coincided with their potential to bind polymeric immunoglobulin; anti-SC reagents inhibited the binding of immunoglobulins to epithelial cells; and SC-containing secretory IgA did not bind to the surface of HT-29 cells.

Toward the identification of a phytocannabinoid-like compound in the flowers of a South African medicinal plant (Leonotis leonurus).

OBJECTIVE: Current global trends on natural therapeutics suggest an increasing market interest toward the use and discovery of new plant-derived therapeutic compounds, often referred to as traditional medicine (TM). The Cannabis industry is currently one such focal area receiving attention, owing to the occurrence of phytocannabinoids (pCBs) which have shown promise in health-promotion and disease prevention. However, the occurrence of pCBs in other plant species are often overlooked and rarely studied. Leonotis leonurus (L.) R. Br. is endemic to South Africa with a rich history of use in TM practices amongst indigenous people and, has been recorded to induce mild psychoactive effects akin to Cannabis. While the leaves have been well-reported to contain therapeutic phytochemicals, little information exists on the flowers. Consequently, as part of a larger research venture, we targeted the flowers of L. leonurus for the identification of potential pCB or pCB-like compounds. RESULTS: Flower extracts were separated and analyzed using high performance thin layer chromatography (HPTLC). A single pCB candidate was isolated from HPTLC plates and, using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), we could successfully group this compound as a fatty amide and tentatively identified as 7,10,13,16-Docosatetraenoylethanolamine (adrenoyl-EA), a known bioactive compound.