Antiparasitic Constituents of Beilschmiedia louisii and Beilschmiedia obscura and Some Semisynthetic Derivatives (Lauraceae)

Waleguele CC, Mba’ning BM, Awantu AF, et al. Antiparasitic Constituents of Beilschmiedia louisii and Beilschmiedia obscura and Some Semisynthetic Derivatives (Lauraceae). Molecules. 2020;25(12): 2862.The MeOH/CH2Cl2 (1:1) extracts of the roots and leaves of Beilschmiedia louisii and B. obscura showed potent antitrypanosomal activity during preliminary screening on Trypanosoma brucei brucei. Phytochemical investigation of these extracts led to the isolation of a mixture of two new endiandric acid derivatives beilschmiedol B (1) and beilschmiedol C (2), and one new phenylalkene obscurene A (3) together with twelve known compounds (4–15). In addition, four new derivatives (11a–11d) were synthesized from compound 11. Their structures were elucidated based on their NMR and MS data. Compounds 5, 6, and 7 were isolated for the first time from the Beilschmiedia genus. Additionally, the NMR data of compound 4 are given here for the first time. The isolates were evaluated for their antitrypanosomal and antimalarial activities against Tb brucei and the Plasmodium falciparum chloroquine-resistant strain Pf3D7 in vitro, respectively. From the tested compounds, the mixture of new compounds 1 and 2 exhibited the most potent antitrypanosomal activity in vitro with IC50 value of 4.91 μM

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Etude de l'insuffisance erectile dans une population d'hommes jeunes et sexuellement actifs au Burkina FasoStudy of erectile dysfuntion in a population of young and sexually active men in Burkina Faso

Objective: This study was carried out among a young population of working men to determine the prevalence of erectile dysfunction (ED) in our environment and to evaluate the patients' knowledge about and attitude towards this problem. Patients and Methods : This study was based on a survey carried out on male subjects aged 18 and above over a period of six months. The survey was done during an annual medical check-up of men working in local companies and some civil servants. Those who agreed to participate in the investigation (855 men), had to complete two questionnaires: the 5-item questionnaire of the International Index of Erectile Function (IIEF-5) evaluating the quality of erectile function and a questionnaire drawn up by our team with the aim of evaluating the participants' knowledge about and their attitude towards the problem of ED. The questionnaires were analyzed using the Epi info program. Results: The 855 subjects that took part in the investigation accounted for 80% of all men that had been asked to participate in the survey. The average age was 37,4 ± 9,1 years; more than two thirds of the participants (78%) were married and 69% were monogamous. The overall prevalence of ED was 47% and we noticed that it increased with age. Three risk factors were identified: age, arterial hypertension and hemorrhoidal disease. Age and arterial hypertension are classic risk factors for ED, while hemorrhoidal disease has so far not been considered as such. In our study, especially for the men interviewed, it has played an important role. 93,2% of the questioned subjects said that they would be ready to consult for ED, whereas in fact only 3,8% had taken medical advice.Conclusion: ED appears to be a real problem, also for younger men, in our environment. However the results of this study cannot be generalised and we are planning to undertake other studies based on the general population which will allow us to draw more valid conclusions and to better organize treatment of these patient. RsumObjectif: Notre tude avait pour objectif de dterminer la prvalence de l'insuffisance rectile (IE) dans notre environnement et d'valuer les connaissances et les attitudes des sujets qui en souffrent. Mthodologie: Il s'agissait d'une enqute transversale sur six mois concernant des sujets gs de 18 ans et plus du monde de travail, ralise au cours d'une visite annuelle des travailleurs des entreprises de la place et de quelques fonctionnaires. Les sujets ayant accept de participer l'enqute (855 hommes), avaient remplir deux questionnaires: la version 5 items de l'International Iindex of Erectile Function (IIEF5), qui value la fonction rectile et, un questionnaire labor par nous mme, dans le but d'valuer les connaissances et les attitudes des enquts, vis vis de l'IE. Les questionnaires ont ensuite t dpouills et analyss sur micro ordinateur l'aide du logiciel Epi info. Rsultats: Les 855 sujets qui ont particip l'enqute reprsentaient 80% de tous ceux qui ont t sollicits. L'ge moyen des enquts tait de 37,4 ± 9,1; plus des 2/3 (78%) taient maris et monogames dans 69%. La prvalence globale note tait de 47% et on a remarqu que celle-ci augmentait avec l'ge. Trois facteurs de risque ont t mis en exergue: l'ge, l'hypertension artrielle (HTA) et la maladie hmorrodaire. Si l'ge et l'HTA sont des facteurs de risque classiques, la maladie hmorrodaire l'est moins; par contre il a t beaucoup invoqu par de nombreux enquts. 93,2% des sujets interrogs seraient prts consulter pour IE, alors que seulement 3,8% l'avaient effectivement dj fait.Conclusion: L'insuffisance rectile s'est rvl comme un problme rel vcu dans notre environnement. Cependant nos rsultats ne peuvent pas tre gnraliss et nous envisageons d'autres tudes, en population gnrale, qui nous permettraient de tirer des enseignements et de mieux organiser la prise en charge de ces patients.African Journal of Urology Vol. 11(4) 2005: 310-31

Sintering behaviors of two porcelainized stoneware compositions using pegmatite and nepheline syenite minerals

Semi-vitreous bodies, with flexural strength of ~78 MPa and water absorption of ~0.4 % for the optimal maturated specimens, were successfully prepared with solid solutions of pegmatite and nepheline syenite, respectively, for the full dense (P) and relatively porous composition (G). Despite the similarity on the bulk chemical composition of the two formulations, it was found that their thermal behaviors were significantly affected by the action of CaO on the flux system considered leading to earlier vitrification of P specimens with high flexural strength as from 1,175 C. Conversely, the flexural strength of G specimens increases progressively with soaking time and temperature development up to 1,225 C. The positive action of 5 mass% of CaO in the vitrification range of pegmatite solution, the relative low temperature of maturation of the semi-vitreous matrices, and the results of water absorption allow us to describe the formulations studied to offer promising potential in the production of sustainable and low-cost porcelainized stoneware. The high strength of P at relatively low temperature could be explained by the matrix-strengthening theory, while the extent of crystallization of G could be ascribed to the mullite theory. © 2013 Akadémiai Kiadó, Budapest, Hungary