Local awareness of and attitudes toward pygmy hippopotamus conservation in the Moa River Island Complex, Sierra Leone.

Abstract The pygmy hippopotamus Choeropsis liberiensis is an Endangered species found only in the Upper Guinea rainforests of West Africa. Using a two-phase approach, with initial semi-structured interviews followed by more extensive questionnaires, we examined local residents’ awareness of and attitudes towards the pygmy hippopotamus along the Moa River near Tiwai Island Wildlife Sanctuary in Sierra Leone. The interviews and questionnaires addressed human–hippopotamus interactions, local knowledge and awareness of pygmy hippopotamus ecology and behaviour, and public attitudes towards hippopotamus conservation. Overall, 22% of questionnaire respondents acknowledged benefits related to hippopotamus conservation; factors affecting the perception of benefits included age, livestock ownership, distance from Tiwai Island and exposure to conservation programmes. The results of this study could be used to inform the conservation of the pygmy hippopotamus and highlight the critical role of local support in the management of threatened species in biodiversity hotspots

Risk of Ischemic Cerebrovascular and Coronary Events in Adult Users of Anticonvulsant Medications in Routine Care Settings

Background: Older‐generation anticonvulsants that highly induce cytochrome P450 enzyme system activity produce metabolic abnormalities that may increase cardiovascular risk. The objective of this study was to evaluate the risk of ischemic cerebrovascular and coronary events in adult new users of anticonvulsants that highly induce cytochrome P450 activity compared with other anticonvulsant agents, as observed in a routine care setting. Methods and Results: This was a cohort study of patients 40 to 64 years old from the HealthCore Integrated Research Database who had initiated an anticonvulsant medication between 2001 and 2006 and had no recorded major coronary or cerebrovascular condition in the 6 months before treatment initiation. Propensity score (PS) matching was used to evaluate ischemic cerebrovascular and coronary risk among anticonvulsant new users. High‐dimensional propensity score (hdPS)–matched analyses were used to confirm adjusted findings. The study identified 913 events in 166 031 unmatched new treatment episodes with anticonvulsant drugs. In a PS‐matched population of 22 864 treatment episodes, the rate ratio (RR) for ischemic coronary or cerebrovascular events associated with highly inducing agents versus other agents was 1.22 (95% CI, 0.90‐1.65). The RR moved to 0.99 (95% CI, 0.73‐1.33) with adjustment for hdPS matching (RR, 1.47; 95% CI, 0.95‐2.28 for cerebrovascular events; RR, 0.70; 95% CI, 0.47‐1.05 for coronary events). Conclusions: In this exploratory analysis, there was no evidence of a consistent and statistically significant effect of initiating anticonvulsants that highly induce cytochrome P450 activity on ischemic coronary or cerebrovascular outcomes compared with other agents, given routine care utilization patterns

Inhibition of cyclo-oxygenase 2 reduces tumor metastasis and inflammatory signaling during blockade of vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) blockade is an effective therapy for human cancer, yet virtually all neoplasms resume primary tumor growth or metastasize during therapy. Mechanisms of progression have been proposed to include genes that control vascular remodeling and are elicited by hypoperfusion, such as the inducible enzyme cyclooxygenase-2 (COX-2). We have previously shown that COX-2 inhibition by the celecoxib analog SC236 attenuates perivascular stromal cell recruitment and tumor growth. We therefore examined the effect of combined SC236 and VEGF blockade, using the metastasizing orthotopic SKNEP1 model of pediatric cancer. Combined treatment perturbed tumor vessel remodeling and macrophage recruitment, but did not further limit primary tumor growth as compared to VEGF blockade alone. However, combining SC236 and VEGF inhibition significantly reduced the incidence of lung metastasis, suggesting a distinct effect on prometastatic mechanisms. We found that SC236 limited tumor cell viability and migration in vitro, with effects enhanced by hypoxia, but did not change tumor proliferation or matrix metalloproteinase expression in vivo. Gene set expression analysis (GSEA) indicated that the addition of SC236 to VEGF inhibition significantly reduced expression of gene sets linked to macrophage mobilization. Perivascular recruitment of macrophages induced by VEGF blockade was disrupted in tumors treated with combined VEGF- and COX-2-inhibition. Collectively, these findings suggest that during VEGF blockade COX-2 may restrict metastasis by limiting both prometastatic behaviors in individual tumor cells and mobilization of macrophages to the tumor vasculature

Lentiviral gene therapy reverts GPIX expression and phenotype in Bernard-Soulier syndrome type C

Bernard-Soulier syndrome (BSS) is a rare congenital disease characterized by macrothrombocytopenia and frequent bleeding. It is caused by pathogenic variants in three genes (GP1BA, GP1BB, or GP9) that encode for the GPIbα, GPIbβ, and GPIX subunits of the GPIb-V-IX complex, the main platelet surface receptor for von Willebrand factor, being essential for platelet adhesion and aggregation. According to the affected gene, we distinguish BSS type A1 (GP1BA), type B (GP1BB), or type C (GP9). Pathogenic variants in these genes cause absent, incomplete, or dysfunctional GPIb-V-IX receptor and, consequently, a hemorrhagic phenotype. Using gene-editing tools, we generated knockout (KO) human cellular models that helped us to better understand GPIb-V-IX complex assembly. Furthermore, we developed novel lentiviral vectors capable of correcting GPIX expression, localization, and functionality in human GP9-KO megakaryoblastic cell lines. Generated GP9-KO induced pluripotent stem cells produced platelets that recapitulated the BSS phenotype: absence of GPIX on the membrane surface and large size. Importantly, gene therapy tools reverted both characteristics. Finally, hematopoietic stem cells from two unrelated BSS type C patients were transduced with the gene therapy vectors and differentiated to produce GPIX-expressing megakaryocytes and platelets with a reduced size. These results demonstrate the potential of lentiviral-based gene therapy to rescue BSS type C

Gene-environment interaction analysis of redox-related metals and genetic variants with plasma metabolic patterns in a general population from Spain: The Hortega Study

Background: Limited studies have evaluated the joint influence of redox-related metals and genetic variation on metabolic pathways. We analyzed the association of 11 metals with metabolic patterns, and the interacting role of candidate genetic variants, in 1145 participants from the Hortega Study, a population-based sample from Spain. Methods: Urine antimony (Sb), arsenic, barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), molybdenum (Mo) and vanadium (V), and plasma copper (Cu), selenium (Se) and zinc (Zn) were measured by ICP-MS and AAS, respectively. We summarized 54 plasma metabolites, measured with targeted NMR, by estimating metabolic principal components (mPC). Redox-related SNPs (N = 291) were measured by oligo-ligation assay. Results: In our study, the association with metabolic principal component (mPC) 1 (reflecting non-essential and essential amino acids, including branched chain, and bacterial co-metabolism versus fatty acids and VLDL subclasses) was positive for Se and Zn, but inverse for Cu, arsenobetaine-corrected arsenic (As) and Sb. The association with mPC2 (reflecting essential amino acids, including aromatic, and bacterial co-metabolism) was inverse for Se, Zn and Cd. The association with mPC3 (reflecting LDL subclasses) was positive for Cu, Se and Zn, but inverse for Co. The association for mPC4 (reflecting HDL subclasses) was positive for Sb, but inverse for plasma Zn. These associations were mainly driven by Cu and Sb for mPC1; Se, Zn and Cd for mPC2; Co, Se and Zn for mPC3; and Zn for mPC4. The most SNP-metal interacting genes were NOX1, GSR, GCLC, AGT and REN. Co and Zn showed the highest number of interactions with genetic variants associated to enriched endocrine, cardiovascular and neurological pathways. Conclusions: Exposures to Co, Cu, Se, Zn, As, Cd and Sb were associated with several metabolic patterns involved in chronic disease. Carriers of redox-related variants may have differential susceptibility to metabolic alterations associated to excessive exposure to metals.This work was supported by the Strategic Action for Research in Health sciences [CP12/03080, PI15/00071, PI10/0082, PI13/01848, PI14/00874, PI16/01402, PI21/00506 and PI11/00726], CIBER Fisio patología Obesidad y Nutrición (CIBEROBN) (CIBER-02-08-2009, CB06/03 and CB12/03/30,016), the State Agency for Research (PID2019-108973RB- C21 and C22), the Valencia Government (GRUPOS 03/101; PROMETEO/2009/029 and ACOMP/2013/039, IDI FEDER/2021/072 and GRISOLIAP/2021/119), the Castilla-Leon Government (GRS/279/A/08) and European Network of Excellence Ingenious Hypercare (EPSS-037093) from the European Commission. The Strategic Action for Research in Health sciences, CIBERDEM and CIBEROBN are initiatives from Carlos III Health Institute Madrid and cofunded with European Funds for Regional Development (FEDER). The State Agency for Research and Carlos III Health Institute belong to the Spanish Ministry of Science and Innovation. ADR received the support of a fellowship from “la Caixa” Foundation (ID 100010434) (fellowship code “LCF/BQ/DR19/11740016”). MGP received the support of a fellowship from “la Caixa” Foundation (ID 100010434, fellowship code LCFLCF/BQ/DI18/11660001). The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.S

Cardiovascular health among diverse Hispanics/Latinos: Hispanic Community Health Study/Study of Latinos (HCHS/SOL) results

Seven national 2020 Strategic Impact Goals for cardiovascular health (Life’s Simple 7 [LS7]) estimates for major ethnic/racial groups are available, but not for diverse Hispanics/Latinos. Herein, we describe and examine LS7 profiles of diverse Hispanic/Latino groups

Cardiovascular health among diverse Hispanics/Latinos: Hispanic Community Health Study/Study of Latinos (HCHS/SOL) results

Seven national 2020 Strategic Impact Goals for cardiovascular health (Life’s Simple 7 [LS7]) estimates for major ethnic/racial groups are available, but not for diverse Hispanics/Latinos. Herein, we describe and examine LS7 profiles of diverse Hispanic/Latino groups

Integrating whole-genome sequencing within the National Antimicrobial Resistance Surveillance Program in the Philippines

Funding: This work was funded by the Newton Fund, Medical Research Council (UK) grant MR/N019296/1, Philippine Council for Health Research and Development project number FP160007. J.S. was partially supported by research grants RR025040 and U01CA207167 from the National Institutes of Health (NIH). S.A. and D.M.A. were additionally supported by the National Institute for Health Research (UK) Global Health Research Unit on genomic Surveillance of AMR(16_136_111) and by the Centre for Genomic Pathogen Surveillance (http://pathogensurveillance.net).National networks of laboratory-based surveillance of antimicrobial resistance (AMR) monitor resistance trends and disseminate these data to AMR stakeholders. Whole-genome sequencing (WGS) can support surveillance by pinpointing resistance mechanisms and uncovering transmission patterns. However, genomic surveillance is rare in low- and middle-income countries. Here, we implement WGS within the established Antimicrobial Resistance Surveillance Program of the Philippines via a binational collaboration. In parallel, we characterize bacterial populations of key bug-drug combinations via a retrospective sequencing survey. By linking the resistance phenotypes to genomic data, we reveal the interplay of genetic lineages (strains), AMR mechanisms, and AMR vehicles underlying the expansion of specific resistance phenotypes that coincide with the growing carbapenem resistance rates observed since 2010. Our results enhance our understanding of the drivers of carbapenem resistance in the Philippines, while also serving as the genetic background to contextualize ongoing local prospective surveillance.Publisher PDFPeer reviewe