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The article presents the discussion on highlighting the systemic racism and inequities remaining prevalent in the society widening the gap of health disparities. Topics include acknowledging the role in historic exclusion and racism evaluating the contributions to current oppressive systems; and advancement for individuals in academic pediatrics being progression toward national leadership roles.

In 2013, the Association of American Medical Colleges created the "Core Entrustable Professional Activities (EPAs) for Entering Residency" to more clearly define the set of activities that entering residents should be able to perform on day 1 of residency without direct supervision. EPA #11 is obtaining informed consent for tests and/or procedures. This EPA acknowledges that an entrustable learner should be able to document a complete consent among other components. The aim of this study is to explore whether incoming pediatric interns demonstrated the behaviors of an "entrustable learner" in the domain of documenting informed consent for a common pediatric procedure. All incoming interns in our program (2007–2017) completed a 6-station Objective Structured Clinical Examination during residency orientation. One of the scenarios involves obtaining parental consent for a lumbar puncture (LP). The researchers determined and agreed what components would be important for a complete and accurately documented consent. A retrospective review of the resident's written informed consents occurred looking for accuracy of documented components. Of the 258 consents reviewed, 8 were complete and accurate. Incoming interns appear to be skilled when completing the basics of the informed consent form such as documenting names, obtaining signatures, and correctly identifying the procedure. However, detailing all the risks of the LP were areas for which they did not demonstrate proficiency. Documenting informed consent is not adequately demonstrated by our learners prior to the beginning of internship. We would recommend specific training before entrusting pediatric interns to obtain LP consent independently. [ABSTRACT FROM AUTHOR]

Abstract Many natural products and medicinal plants have been tested experimentally for validation of their reported folkloric efficacies. South Africa has abundant plant biodiversity and medicinal plants are still widely used in most parts of the country for the treatment of common neurodegenerative disorders (NDDs). However, very few studies have reported on the validation of South African medicinal plants (SAMPs) used in traditional, complementary and alternative medicine (TCAM) for the treatment of NDDs. Extensive testing provides the basis for clinical trials which progressively lead to the development of affordable, indigenous and readily available products for preventing or treating NDD including Parkinson's disease (PD), one of the most common central nervous system (CNS) disorders among the elderly often characterized by the progressive loss of dopaminergic neurons (DNs) or dopamine-producing cells in the substantia nigra of the midbrain. In this study, several databases were searched to identify active compounds in SAMPs known to potentially protect neurons from progressive damage as seen in most NDDs. Our search results showed many commonly used SAMPs and their possible mechanisms of action including prevention of neuronal death by inhibition of Caspase-3 activation, MAO-B enzyme inhibition as well as restoration of glutathione content in cells. Most of the observed effects relate to the protection of DNs from degeneration, indicating the potential use of these compounds as antiparkinsonian agents. This review article therefore identifies and presents research gaps on how indigenous SAMPs could be studied more extensively for their chemical constituents and bioactivity against age-related NDDs such as PD. [ABSTRACT FROM AUTHOR]

The grand vision was launched in 2013 originally as the ‘One Belt, One Road’ (OBOR) initiative. OBOR involves China underwriting billions of dollars of infrastructure investment linking countries in Europe, Asia, and Africa. At the centre of the plan are two physical routes: the Silk Road Economic Belt, stretching from Asia to Europe; and the twenty-first century Maritime Silk Road that begins in China and passes along the Indian Ocean littoral to East Africa and then Europe. The nature of this economic initiative seeks to create a community of shared prosperity, in which nations can share mutual benefits and coexist peacefully along the trade routes. The paper examines China–Africa relations, centring on the possibility of expanding the OBOR initiative to cover more African nations. Also, it examines the investment environment of Africa and its significant for more African slot. Africa should provide enabling business environment to grasp the OBOR’s opportunities. [ABSTRACT FROM PUBLISHER]

Highlights: [•] The genotoxicity of selected commercial food products in Finland was evaluated. [•] Some food products showed potential as sources of both direct and indirect mutagens. [•] The mutagenic impact was not due to histidine release. [•] No DNA damage was detected in HepG2 cells by food extracts with mutagenic potential. [•] Genotoxicity was not confined to a particular food type or method of processing. [Copyright &y& Elsevier]

Abstract: In this study, the effects of bitter yam sapogenin extract or commercial diosgenin on intestinal disaccharidases and some renal enzymes in diabetic rats were investigated. Diabetic male Wistar rats were fed diets supplemented with 1% sapogenin extract or commercial diosgenin for 3 weeks. Plasma glucose, intestinal disaccharidases and the activities of transaminases, acid phosphatase, glucose-6-phosphatase, ATP citrate lyase, glucose-6-phosphate dehydrogenase and pyruvate kinase were assessed for the level of metabolic changes in the kidney of diabetic rats. Sapogenin extract or commercial diosgenin supplementation resulted in a significant decrease in lactase and maltase activities in all three regions of the intestine compared to the diabetic control group. However, the test diets significantly reduced intestinal sucrase activity in the proximal and mid regions. Test diets supplementation resulted in a significant decrease in the activities of the transaminases compared to the normal and diabetic control groups. The activity of glucose-6-phosphatase was significantly increased while the activities of ATP citrate lyase, pyruvate kinase and glucose-6-phosphate dehydrogenase were significantly reduced in the kidney of the diabetic control rats compared to the normal group. Test diets supplementation did not significantly alter glucose-6-phosphatase, ATP citrate lyase and pyruvate kinase activities compared to the diabetic control. However, there was a significant increase in glucose-6-phosphate dehydrogenase activity toward the normal group. In conclusion, the consumption of bitter yam sapogenin extract or commercial diosgenin demonstrated hypoglycemic properties, which are beneficial in diabetes by reducing intestinal disaccharidases activities; however, bitter yam sapogenin extract may adversely affect the integrity of kidney membrane. [Copyright &y& Elsevier]

Abstract: This study compares the effectiveness of various image enhancement filters for improving the perceived visibility of coloured digital natural images for people with visual impairment. Generic filters were compared with Peli’s adaptive enhancement and adaptive thresholding and custom-devised filters based on each subject’s contrast sensitivity loss. Subjects with low vision made within filter rankings followed by between filter ratings. In general, subjects preferred filters with lower gains. Unsharp masking resulted in a significant increase in perceived visibility for some image types (p ⩽0.05) while Peli’s adaptive enhancement, edge enhancement and histogram equalization resulted in borderline improvements. Adaptive thresholding and the custom devised filter did not result in overall improvements in perceived visibility. [Copyright &y& Elsevier]

In this study, the effect of yam steroidal sapogenin extract on intestinal morphology in streptozotocin-induced diabetic rats was examined. Diabetic male Wistar rats (n = 32) were fed diets supplemented with 1% bitter yam steroidal sapogenin extract or commercial diosgenin for three weeks. The effect on intestinal morphology was assessed. The induction of diabetes significantly increased villus length and crypt depth compared to the normal group. Supplementation of the diet with sapogenin extract or commercial diosgenin significantly increased villus width compared to the diabetic controls. The dietary supplements also significantly decreased crypt depth towards that of the normal controls. This study shows that the feeding of bitter yam steroidal sapogenin extract to diabetic rats may result in alterations in the intestinal morphology. [Copyright &y& Elsevier]

Bitter yam (Dioscorea polygonoides) steroidal sapogenin extract and commercial diosgenin were administered to diabetic rats for 21 days. Plasma glucose and lipids were assessed. Liver lipid distributions were also determined.The two dietary supplements fed to diabetic rats resulted in significant decreased body weight gain. The test diets significantly lowered plasma glucose and total cholesterol. Sapogenin extract supplement significantly lowered plasma total triglycerides. Plasma and liver VLDL+LDL-cholesterol were significantly reduced while the HDL fraction was increased in diabetic rats fed the test supplements. These results showed that the consumption of the two supplements maybe useful in the management of hypercholesterolemia often associated with diabetes. [Copyright &y& Elsevier]

Streptozotocin-induced diabetic rats were maintained for four weeks on extracts of yam or dasheen or commercial linamarin. The levels of blood glucose, digestive and membrane-bound enzymes of the intestine were determined. Rats fed commercial linamarin significantly lowered blood glucose level compared to the diabetic rats fed normal diet. Feeding of commercial linamarin to diabetic rats significantly decreased the activity of intestinal amylase compared to normal rats. Dasheen extract or commercial linamarin significantly increased the activities of intestinal disaccharidases compared to the diabetic rats fed normal diet. Na+ /K+ ATPase activity in the lower segment of the intestine was significantly reduced in diabetic rats compared to normal rats. In the upper segment of the intestine, yam or dasheen extract or commercial linamarin supplementation increased the activity of this enzyme above normal. These observations show that the hypoglycemic property of cyanoglucoside extract from dasheen and to a lesser extent yam, could be due to other chemical constituents of the extract and this needs further investigation. [Copyright &y& Elsevier]

Neuroblastoma is a solid neuroendocrine tumour located outside the cranial cavity and contributes about 15% of all cancer‑associated deaths in children. Treatment of neuroblastoma is quite challenging and involves the use of chemotherapy, surgery and radiotherapy. Despite treatment strategies, systemic toxicity are setbacks to patient well-being, hence the need for a new and affordable approach. Medicinal plants are of importance in the field of drug discovery for cancer as some notable anti-cancer agents have been isolated from them. In the present study, the anti-cancer activity of aqueous extract of Carpobrotus edulis (C. edulis), a ground-creeping edible medicinal plant was investigated in SK-N-BE(2) and SH-SY5Y neuroblastoma cells. The effect of C. edulis on cell viability and survival was determined using MTT (3-[4,5-dimethylthiazol-2-yl]−2,5 diphenyltetrazolium bromide) and clonogenic assays respectively. Apoptosis was determined using a Caspase-9 assay kit and flow cytometry was used to measure intracellular reactive oxygen species (ROS) and depolarization of mitochondrial membrane potential. The results show that C. edulis inhibits cell viability (IC 50 of 0.86 mg/ml and 1.45 mg/ml for SK-N-BE(2) and SHSY5Y cells respectively) and colony formation in the neuroblastoma cells as well as induce apoptosis, which is evidenced by an increase in caspase-9 activity in the cells. C. edulis also led to a loss of mitochondrial membrane potential and increased production of ROS. Collectively, these results suggest that C. edulis induces cell death via induction of mitochondrial‐mediated apoptosis and accumulation of intracellular ROS, thus providing a rationale for further investigations. [ABSTRACT FROM AUTHOR]

Health inequities disproportionately impact children of color in the United States. Research demonstrates that a diverse physician workforce that reflects the demographic profile of the United States population has been associated with better health outcomes and physicians of color are more likely to work in communities that are medically underserved. Therefore, a key driver to reducing health inequities is recruiting a physician workforce that reflects the racial/ethnic composition of the population. Although efforts on increasing UIM applicants and matriculants into medical school and more recently, graduate medical education (GME) programs have shown some small successes, there has still not been significant change in decades. This narrative review examined the historical trends and current landscape of recruitment in GME to better understand the barriers and facilitators that continue to exist and identify successful interventions that might serve as a model to support recruitment of UIM applicants. There is evidence for racial disparities and bias in traditional residency selection metrics (USMLE, Clerkship Evaluations, MSPE, AOA status, etc.) and a need for more holistic recruitment strategies. Along with implementing new holistic recruitment practices, there is a need for ongoing research and collaboration to study inclusive and equitable learning environments and assessments that will eliminate racial disparities in educational outcomes. Additionally, there must be better longitudinal data utilization and transparency across Electronic Residency Application Services (ERAS) and National Resident Matching Program (NRMP) for accountability and tracking of interventions. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) can cause severe illness in older adults. A combination vaccine containing Ad26.RSV.preF and purified recombinant RSV preF protein has previously demonstrated efficacy and tolerability in older adults. We report results of a dose-ranging study to determine immunogenicity and safety of different doses of the Ad26.RSV.preF component in the combined Ad26.RSV.preF/RSV preF protein vaccine to support Ad26.RSV.preF drug product release and stability specifications. In this randomized, double-blind, placebo-controlled, phase 2a study, adults aged ≥60 years in good or stable health were randomly assigned within 1 of 3 cohorts to receive either placebo or Ad26.RSV.preF/RSV preF protein, composed of different doses of Ad26.RSV.preF with a fixed dose of RSV preF protein (150 μg). Ad26.RSV.preF doses in Cohort 1 (4 dose-down groups) ranged from 3.7 × 109 to 1.0 × 1011 viral particles (vp). Doses in Cohorts 2 and 3 (2 dose-up groups, each) ranged from 1.0 to 1.6 × 1011 vp. Primary endpoints were immunogenicity (RSV preF protein antibody titers) for Cohort 1 and safety (solicited local and systemic adverse events [AEs] and unsolicited AEs) for Cohorts 2 and 3. Immunogenicity analyses (RSV preF protein antibody titers, RSV A2 neutralizing antibodies, and RSV-F–specific interferon-γ enzyme-linked immunosorbent spot) were performed on the day of vaccination and 14 days, 3 months, and 6 months postvaccination. Safety was monitored from vaccination until study end. Overall, 454 participants were enrolled and received 1 dose of study vaccine or placebo (Cohort 1, n = 226; Cohort 2, n = 124; Cohort 3, n = 104). No substantial differences in measured immune responses were observed between lower or higher Ad26.RSV.preF doses compared with Ad26.RSV.preF 1.0 × 1011 vp across all postvaccination time points. All Ad26.RSV.preF doses between 3.7 × 109 vp and 1.6 × 1011 vp were well tolerated, with no safety issues identified. Results of this dose-ranging study may be used to inform the refinement of Ad26.RSV.preF drug product release and stability specifications. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04453202 • Respiratory syncytial virus (RSV) can cause severe illness in older adults. • An Ad26.RSV.preF/RSV preF protein vaccine was safe and effective in older adults. • Varying doses of the Ad26.RSV.preF component combined with fixed doses of the RSV preF component were evaluated. • All Ad26.RSV.preF doses, with fixed RSV preF, induced similar immune responses. • All Ad26.RSV.preF doses were well tolerated, with no safety issues identified. [ABSTRACT FROM AUTHOR]

B Methods and materials: b The total heterotrophic and staphylococcus aureus counts were determined using plate count agar and mannitol salt agar respectively, while phenotypic identification of MRSA was investigated with mannitol-oxacillin agar. B Results: b The majority (75%) of samples investigated were found to harbour Staphylococcus aureus, with Staphylococcus aureus counts ranging from 0.0±0.0×10 SP 3 sp to 300±0.0×10 SP 3 sp cfu/g. Rice, meat-pie, spaghetti and doughnut were observed to be the most heavily contaminated with Staphylococcus aureus. [Extracted from the article]

An Accreditation Council for Graduate Medical Education Common Program requirement states that a training program must evaluate resident performance in a timely manner and use multiple evaluators. Peer evaluation is one tool used by many programs to fulfill this requirement. Peer evaluation is critical to the development and training of residents because it allows for the assessment of cognitive and noncognitive skills not necessarily observed by faculty. A literature review showed that effective feedback should be performance-focused, specific, based directly on observable, or objective data, neutral, identify a plan for improvement. The purpose of this study was to evaluate the quality of open-ended feedback provided to pediatric residents by their peers throughout their clinical rotations. At our institution, pediatric residents are asked to complete a peer evaluation form on all residents that they have worked with during their rotation. The residents received no formal training on giving peer feedback. The form is a series of Likert scaled questions and an open-ended feedback section. Based on our literature review, we created a rubric that assessed the degree to which the open-ended comments were specific (low, moderate, or high), actionable (yes or no), and objective (low, moderate, or high). Two blinded reviewers retrospectively analyzed 1368 peer feedback comments received by 26 graduating pediatric residents during their 3-year training period. Cohen's kappa for each criterion demonstrated high inter-rater reliability. Our analyses determined that, on average, 59% of the comments were rated moderately or highly specific (?=0.834), 3% were rated actionable (?=0.969), and 92% were rated moderately or highly objective (?=0.935) when evaluated separately against each criterion in the rubric (e.g. specificity alone). When analyzing the overall quality of each comment, less than 5% of comments (?=0.958) were determined to be specific (moderate or high), actionable, AND objective (moderate or high). While a majority of comments were evaluated to be specific and/or objective, we found the greatest disparity in feedback quality was a lack of actionable feedback. These results indicate residents-in-training need development on how to improve the quality of feedback they provide to their peers, particularly in the area of actionable information. Future efforts should focus on creating and evaluating strategies that elicit higher quality feedback. [ABSTRACT FROM AUTHOR]

Le FIL, inhibiteur oral préférentiel de la Janus kinase 1, est approuvé à des doses de 100 mg (FIL100) et 200 mg (FIL200) pour le traitement de la PR active modérée à sévère. Les analyses de sécurité intégrées des essais cliniques précédents ont montré que la sécurité et la tolérance sont similaires entre les doses de FIL, avec une incidence plus faible de zona avec FIL100 par rapport à FIL200.1 L'objectif de cette étude était de fournir une mise à jour du profil de sécurité à long terme du FIL jusqu'à une exposition médiane (maximale) de 4,3 (8,3) ans. Les données FIL sur la PR ont été intégrées à partir de 7 essais cliniques : les études de phase 2 DARWIN (NCT01888874 , NCT01894516), les études de phase 3 FINCH (NCT02889796 , NCT02873936 , NCT02886728) et les études d'extension à long terme DARWIN 3 (NCT02065700) et FINCH 4 (NCT03025308). Le taux d'incidence ajusté en fonction de l'exposition (TIAE)/100 patients-année d'exposition (PAE), censurés au moment du premier événement, a été déterminé pour les événements cardiovasculaires indésirables majeurs (ECM), les événements thromboemboliques veineux (TEV), les événements thrombotiques artériels systémique (TAS), les cancers de la peau non-mélanome (CCNM), les tumeurs malignes non-CCNM, les zona, les infections graves et les décès. Les données provenaient d'études terminées et jusqu'au 8 mai 2023 pour FINCH 4. ECM et TEV n'incluaient que les événements ayant fait l'objet d'une adjudication avec une date limite de données fixée au 8 mai 2023. La population traitée était composée de 3691 patients avec 14 127 PAE. La durée d'exposition médiane (max) était 4,3 (8,3) ans pour l'ensemble des patients, 3,6 (8,1) années pour le groupe FIL100 et 4,4 (8,3) années pour le groupe FIL200. Les données démographiques et les caractéristiques de la maladie au départ étaient similaires dans les deux groupes. L'incidence des événements indésirables d'intérêt, incluant ECM, TEV, TAS, CCNM, tumeurs malignes non-CCNM, infections graves, zona et mortalité toutes causes confondues, était comparable entre les données censurées en 2022 et l'analyse actuelle (Tableau 1). En raison de la conception des études, la durée d'exposition était plus courte dans le groupe FIL100 (5202,2 PAE) que dans le groupe FIL200 (8924,5 PAE) ; les comparaisons des TIAE entre les groupes de traitement doivent donc être faites avec prudence. Le TIAE (intervalle de confiance à 95 % [IC])/100 PAE d'infections graves était de 2,2 (1,8–2,6) et de 1,7 (1,5–2,0) dans les groupes FIL100 et FIL200, respectivement. Le TIAE (IC à 95 %)/100 PAE du zona était de 1,1 (0,8–1,4) pour FIL100 et de 1,4 (1,2–1,7) pour FIL200 (Tableau 1). Sur 312 semaines, le risque de mortalité toutes causes confondues était similaire pour FIL100 et FIL200 (Figure 1). Dans cette analyse de sécurité intégrée actualisée, le profil de sécurité de FIL reste stable dans le temps et similaire à celui de l'analyse précédente. Aucune nouvelle information de sécurité concernant les événements indésirables d'intérêt n'a été identifiée dans la population globale atteinte de PR de cette analyse intégrée. [ABSTRACT FROM AUTHOR]

Le filgotinib (FIL) est un inhibiteur préférentiel de JAK1 pour le traitement de la polyarthrite rhumatoïde (PR) modérée à sévère. FINCH 4 (NCT03025308) est une étude d'extension ouverte à long terme en cours, conçue pour évaluer la sécurité et l'efficacité de FIL chez les patients atteints de PR qui ont terminé une étude pilote de phase 3, FINCH 1, 2 ou 3,1–3 Cette analyse intermédiaire post hoc de FINCH 4 caractérise l'efficacité à long terme de FIL administré en monothérapie (MONO) ou en association (ASSO). Les patients recrutés dans FINCH 4 à partir de FINCH 1, 2 et 3 ont été regroupés et évalués selon le groupe de traitement :FIL 200 mg (FIL200) ou FIL 100 mg (FIL100) administré en MONO ou en ASSO. L'ASSO et la MONO ont été définies comme FIL avec ou sans méthotrexate ou un autre traitement de fond conventionnel à partir de l'inclusion dans FINCH 4. Les patients qui sont passés de la MONO à l'ASSO ou inversement, avec une interruption totale du traitement de fond > 28 jours, ont été exclus des analyses. Les patients passés de l'ASSO à la MONO ≤ 28 jours ont été inclus dans le groupe ASSO. La variation de la moyenne des moindres carrés (LS-Mean) du score d'activité de la maladie sur 28 articulations avec la protéine C-réactive (DAS28-CRP) par rapport à la valeur de base de l'étude parentale a été analysée à l'aide d'un modèle à effets mixtes pour mesures répétées, incluant des variables pour : la valeur de base de l'étude parentale, l'étude parentale, l'exposition antérieure au FIL (binaire), le traitement, la visite et l'interaction entre le traitement et la visite. Les taux de réponse non stratifiés de DAS28-CRP < 2,6 et ≤ 3,2 ont été analysés sur la base des cas observés (CO) et de l'imputation des non-répondeurs (INR). Au total, 2273 patients ont été inclus dans les analyses (771 :FIL200 ASSO, 520 :FIL200 MONO, 728 :FIL100 en ASSO et 254 :FIL100 MONO) avec une date limite de données au 8 mai 2023. À la semaine 216, la variation LS-Mean (IC à 95 %) du DAS28-CRP par rapport à la valeur initiale de l'étude parentale était de –3,0 (–3,1, –2,9) dans le groupe FIL200 ASSO, de –3,3 (–3,4, –3,2) dans le groupe FIL200 MONO, de –2,8 (–2,9, –2,7) dans le groupe FIL100 ASSO et de –2,9 (–3,1, –2,7) dans le groupe FIL100 MONO (Figure 1). La proportion de patients ayant atteint un taux de DAS28-CRP < 2,6 dans les groupes FIL200 ASSO, FIL200 MONO, FIL100 ASSO et FIL100 MONO était respectivement de 27,1 %, 25,6 %, 21,6 % et 20,5 % avec l'analyse INR (Figure 2A), et de 60,2 %, 73,5 %, 50,2 % et 60,5 %, respectivement, avec l'analyse CO (Figure 2B). La proportion de patients ayant atteint un taux de DAS28-CRP ≤ 3,2 était respectivement de 35,4 %, 30,4 %, 30,9 % et 24,8 % avec l'analyse INR, et de 78,7 %, 87,3 %, 71,9 % et 73,3 %, respectivement, avec l'analyse CO. Les résultats intermédiaires de l'étude FINCH 4 montrent que dans tous les sous-groupes de traitement, un taux de DAS28-CRP < 2,6 a été atteint par 20,5 à 27,1 % des patients à la semaine 216 selon l'analyse INR, et par 50,2 à 73,5 % selon l'analyse CO. Cette dernière analyse indique que les améliorations du DAS28-CRP se sont maintenues dans le temps, que FIL ait été administré en MONO ou en ASSO. [ABSTRACT FROM AUTHOR]

Diabetes mellitus, as a result of microvascular and macrovascular injury, causes organ dysfunction in a wide variety of tissues. The objective of this study was to investigate the effect of combined inositol hexakisphosphate and inositol supplement on renal and pancreatic integrity in type 2 diabetic rats. Thirty male Sprague-Dawley rats were divided into five groups ( n = 6 per group). Type 2 diabetes was induced in three groups using high-fat diet combined with a single dose of streptozotocin (35 mg/kg body weight, intraperitoneally). Two of the diabetic groups were treated with combined IP6 and inositol or glibenclamide. Serum biochemical markers of kidney damage kidney, antioxidant status (superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) and lipid peroxidation were measured. Histomorphological and morphometric examinations of the H&E stained pancreas were also carried out. The administration of combined IP6 and inositol supplement resulted in 64% and 27% increase in CAT activities and GSH levels respectively and a 25% decrease in lipid peroxidation level compared to the diabetic control. Serum uric acid, creatinine and BUN levels in the combination treated group was comparable to the normal control. Examination of H&E stained pancreatic sections showed a significant increase (107%) in the number of islets in the combined IP6 and inositol treated group compared to the untreated diabetic group. Overall, the treatment of type 2 diabetic rats with combined IP6 and inositol supplement resulted in the improvement of renal and pancreatic function. [ABSTRACT FROM AUTHOR]

Abstract: In this study, three steroidal sapogenins (Δ3 diosgenin, diosgenin, and pennogenin) and the phytosterols, stigmasterol and β-sitosterol were isolated from Jamaican bitter yam, Dioscorea polygonoides. Their effects on fasting blood glucose and intestinal amylase and ATPases in streptozotocin-induced diabetic rats were studied. The diabetic rats (fed supplemented and unsupplemented diets) lost weight significantly compared to the normal group. There was a significant increase in the activity of α-amylase in the proximal region of the small intestinal mucosa of diabetic rats fed sapogenin extract or commercial diosgenin. However, this did not result in increased fasting blood glucose. Instead, supplementation of the diet with bitter yam sapogenin extract significantly decreased fasting blood glucose compared to the diabetic group. Supplementation of the diet with bitter yam sapogenin extract or commercial diosgenin significantly reduced Na+–K+-ATPase activity in all three regions compared to the diabetic control group. Commercial diosgenin supplementation resulted in a significant increase in Ca2+ ATPase activity in proximal region compared to the diabetic control and bitter yam sapogenin extract groups. The effect of bitter yam sapogenin extract or commercial diosgenin on intestinal Na+–K+-ATPase activity could account for their hypoglycemic properties. However, there was adverse effect on the body weight. [Copyright &y& Elsevier]

Les inhibiteurs des Janus kinases (JAK) constituent une option thérapeutique précieuse pour atteindre les objectifs de rémission ou de faible niveau d'activité de la polyarthrite rhumatoïde (PR) chez les patients avec une réponse inadéquate (IR) ou une intolérance à ≥ 1 traitement de fond antirhumatismal (DMARD) conventionnel de synthèse. Le filgotinib (FIL) est un inhibiteur préférentiel de JAK1, indiqué dans le traitement de la PR modérée à sévère et disponible sous deux dosages. Objectif : évaluer l'efficacité à long terme de deux doses de FIL dans les populations de patients inclus dans l'essai FINCH 4. Dans cette analyse intermédiaire, l'efficacité (imputation des non-répondeurs) de FIL 200 mg (FIL200) et de FIL 100 mg (FIL100) a été évaluée entre le début de l'étude d'extension à long terme (LTE) et la Semaine (S) 156 chez des patients présentant une réponse inadéquate au méthotrexate (MTX-IR) ou aux produits biologiques (bDMARD-IR), ayant participé aux études initiales FINCH 1 (NCT02889796) et 2 (NCT02873936), respectivement, et ayant reçu au moins 1 dose de FIL dans l'étude FINCH 4 (NCT03025308). Le plan de l'étude, les caractéristiques initiales et les résultats à S48 des patients présentant une MTX-IR1 ou une bDMARD-IR2 ont été rapportés précédemment. Chez les patients MTX-IR ou bDMARD-IR ayant reçu FIL200 ou FIL100 dans les études initiales, le taux de rémission à S156 basé sur les critères Boolean 1,0 était de 20,5 % et 15,8 %, et 18,2 % et 8,9 %, respectivement. Le taux de rémission avec FIL200 et FIL100 à S156 basé sur les critères Boolean 2,0 était légèrement plus élevé : +4,2 % et +4,9 % chez les patients MTX-IR, et +1,5 % et +2,4 % chez les patients bDMARD-IR, respectivement. Chez les patients randomisés à nouveau pour recevoir le FIL au début de l'étude LTE, le taux de rémission était également plus élevé avec Boolean 2,0 vs Boolean 1,0. La rémission à long terme selon les critères Boolean était maintenue chez les patients MTX-IR (Figure 1) et chez les patients bDMARD-IR jusqu'à S156 avec FIL200 et FIL100, quel que soit leurs antécédents de traitement par le FIL. Les résultats obtenus pour un score d'activité de la maladie avec la protéine C-réactive (DAS28-CRP) < 2,6, un indice clinique d'activité de la maladie (CDAI) ≤ 2,8, et un indice clinique d'activité de la maladie simplifié (SDAI) ≤ 3,3, ainsi que les modifications moyennes par rapport aux valeurs de départ des études initiales de l'indice d'incapacité du questionnaire d'évaluation de la santé (HAQ-DI) et de la douleur sont présentés (Tableau 1). Des résultats d'efficacité similaires ont été observés pour une faible activité de la maladie et les critères de réponse de l'ACR (American College of Rheumatology). Dans l'étude FINCH 4, l'efficacité de FIL200 et FIL100 était maintenue jusqu'à S156 dans ces populations de patients cliniquement pertinentes. L'utilisation des critères Boolean 2,0 a permis de classer davantage de patients en rémission, conformément à la fourchette rapportée dans l'étude de validation [1]. [ABSTRACT FROM AUTHOR]

The neuroprotective effects of closed polycyclic cage molecules such as NGP1-01, memantine and amantadine have been extensively explored. These effects are mostly linked to the antagonism of the N -methyl- d -aspartate (NMDA) receptor- and the blockage of voltage gated calcium channels (VGCC). The synthesis of structurally related open and rearranged cage derivatives has been studied in depth. However, very little is known on their neuroprotective effects. In this study, a series of open and rearranged polycyclic cage molecules containing a norbornane derived scaffold were synthesised and evaluated for cytotoxicity, neuroprotection and calcium blocking effects via the NMDA receptor and VGCC on neuroblastoma cells at a 10 μM concentration. All compounds showed negligible cytotoxicity and were able to significantly attenuate MPP+-induced neurotoxicity between 26.07 ± 12.50% to 48.42 ± 0.76%, with compound 14 showing the best neuroprotective effect. In comparison to known NMDA receptor antagonists, all compounds demonstrated moderate to excellent calcium blocking effects of 26.50 ± 2.28 to 72.95 ± 3.38%. Docking studies suggest that these compounds are able to show significant NMDA receptor channel blocking ability since they bind in a comparable manner to the crystallographic pose of MK-801 inside the NMDAR ion channel. Some compounds were also able to attenuate calcium influx through VGCC channels between 21.28 ± 3.69% to 50.34 ± 7.67%. Compound 4 and 15 showed the highest inhibition of calcium influx at the VGCC and NMDA receptor, respectively. The compounds exhibiting good cytotoxicity-, neuroprotective- and calcium blocking profiles could potentially act as neuroprotective agents to clinically benefit people suffering from neurodegenerative disorders. Image 1 • Synthesis of open- and rearranged polycyclic cage molecules are reported. • All compounds (1 – 15) showed minimal toxicity towards neuroblastoma cells at 10 μM. • The compounds were able to attenuate MPP+-induced neurotoxicity. • Significant attenuation of calcium influx at the NMDA receptor and VGCCs observed. • A number of compounds displayed multifunctional neuroprotective abilities similar to NGP1-01. [ABSTRACT FROM AUTHOR]

The leaves of Justicia flava are traditionally used in the South of Nigeria to prevent preterm births. Aim of the study : In this study, the activity of the methanol leaf extract of J. flava (JF) was investigated on uterine contractility in non-pregnant and pregnant isolated mouse tissues. The effects on spontaneous, oxytocin, and KCl-induced contractions were determined. The effects in calcium-free media were also determined. Possible mechanisms of activity were investigated using receptor and channel modulators. Mass spectrometric analysis was additionally performed on the leaf extract to identify secondary metabolites. JF was observed to inhibit spontaneous, oxytocin and high KCl-induced uterine contractility. JF also inhibited contractions in Ca2+-free media. JF was found to exert its inhibitory effect via interaction with inositol triphosphate and ryanodine receptors and also through modulation of K+- channels. Lignans and alkaloids were identified with the lignans being the most abundant in JF. JF has been shown to potently inhibit uterine contractions in non-pregnant and pregnant isolated mouse uterus. The inhibitory activity of JF has been shown to occur via blockade of extracellular and intracellular calcium entry and these effects may be due to the lignans identified in - JF. JF has therefore been shown in this study to be a lead plant in the discovery of new drugs with uterine inhibitory activity. Image 1 [ABSTRACT FROM AUTHOR]

Abstract The mediator of dioxin toxicity, aryl hydrocarbon receptor (AHR), has also important physiological functions. Selective AHR modulators (SAHRMs) share some effects of dioxins, except for their marked toxicity. We recently characterised toxicologically two novel SAHRMs, prodrugs IMA-08401 and IMA-07101 in rats, demonstrating that they are far less deleterious than the most toxic AHR-agonist, TCDD. Here, we analysed the in vitro toxicity and in silico AHR binding of the respective active, deacetylated metabolites, IMA-06201 (N-ethyl- N -phenyl-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-06504 (N-(4-trifluoromethylphenyl)-1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide). In H4IIE rat hepatoma cells, IMA-06201 and IMA-06504 induced CYP1A1 with comparable potencies and efficacies to those of TCDD. They had little effect on cell viability as assessed by LDH leakage and MTT reduction assays, and were not mutagenic in the Ames test, but IMA-06504 elicited a maximally 2.7-fold increase in micronuclei. Molecular docking simulations showed that similar to TCDD, they occupy the central region of AHR ligand binding cavity. Hence, while showing low to negligible in vitro toxicity, these novel SAHRMs bind to the AHR qualitatively in a similar fashion to TCDD, and appear comparably powerful AHR agonists. Combined with our earlier results demonstrating that they seem considerably less toxic in vivo than TCDD, these compounds are thus highly interesting new SAHRMs. Highlights • IMA-06201 and IMA-06504 are selective AHR modulators. • As CYP1A1 inducers, they appear comparable to TCDD in potency and efficacy. • They also show low to negligible cytotoxicity and mutagenicity in vitro. • Based on in silico modelling, their binding to the AHR resembles that of TCDD. • Therefore, they have potential as drug compound candidates and research tools. [ABSTRACT FROM AUTHOR]

The lack of a suitable decision framework for the governance of public-private partnership (PPP) projects in Africa, especially Ghana, is a major setback to project success, retarding sustainable development. This study develops a hierarchical decision framework for prioritizing project governance factors and their relationships using the Decision Making Trial and Evaluation Laboratory (DEMATEL) method. We employ 30 experts to evaluate two main PPP governance factors and eleven subfactors. We found that contractual governance factors of PPP are more prominent than noncontractual ones for sustainable PPP projects. However, noncontractual governance factors have the highest net effect on contractual factors. Again, policy diffusion is the contractual factor with the highest net effect, while best practice team norm is the noncontractual factor with the highest net effect. Additionally, effective risk allocation is the most prominent contractual subfactor of PPP, while effective communication of project information is the most prominent noncontractual governance factor. The results imply that PPP project managers should improve governance factors for the sustainable development of PPP projects in Africa. However, they should emphasize the prominent and high net effect governance factors but not wholly disregard the less prominent ones. • Contractual governance factors of PPP are more prominent than noncontractual ones. • Noncontractual governance factors have the highest net effect on contractual factors. • Policy diffusion is the contractual factor with the highest net effect. • Best practice team norm is the noncontractual factor with the highest net effect. [ABSTRACT FROM AUTHOR]