Antipyretic effect of crude methanolic extract of Mytragyna speciosa in mice.

Mitragyna speciosa is a species of tropical indigenous plant that can be found mainly in Southeast Asia. This study aims to ascertain the existence of antipyretic properties of the crude methanolic extract of Mitragynaspeciosa, and determine its effective dose against Brewer's yeast-induced pyrexia in mice. Thirty BALB/c mice were randomly divided into three treatment groups and two control groups. Pyrexia was induced by subcutaneous injection of 30% Brewer's yeast. Rectal temperature was recorded before and 18 h after induction of pyrexia every 30 min ofr 5 h. All groups treated with the crude methanolic extracts of Mitragynaspeciosa (50 mg/kg), 200 mg/kg were observed to produce signifivantreduction of rectal temperture as compared to the negative control group at different times. Ketoprofen at the dosage of 1 mg/kg coused significant (p<0.001) inhibition of fever from 0.5 to 5.0 h after treatment. In conclution, the crude methanolic extract of Mitragyna speciosa possessed dose-dependent antipyretic properties in mice. The antipyretic effective dose of the crude methanolic extract of Mitragyna speciosa was 100 mg/kg

Antipyretic effect of mitragynine and crude methanolic extract of Mitragyna speciosa Korth. in mice

Mitragyna speciose Korth., also known as ketum or kratom, is a tropical plant native to Southeast Asia. Mitragynine is its major active alkaloid. It is traditionally used as treatment for various conditions, including fever. The crude extract of M. speciosa leaves has been proven to have anti-inflammatory and analgesic properties. In general, M. speciosa induces a dose-dependent effect, inducing a stimulant effect at low dose and an opioid-like effect at a high dose. This study was conducted to determine the antipyretic effect of mitragynine and methanolic extract of M. speciosa (MSM) using mice as an in vivo pyretic model. Eighty mice were divided into 8 groups: 6 treatment groups (mitragynine: 5, 10, and 20 mg/kg; MSM: 50, 100, and 200 mg/kg) and 2 control groups (20% Tween 80 in 0.9% NaCl; ketoprofen 1 mg/kg). Eighteen hours after induction of pyrexia by inoculation of yeast, rectal temperature was measured every half an hour for 5 hours. Compared to the negative control group, all groups treated with either mitragynine or MSM had significant reduction of rectal temperature at different points of time. The positive control group treated with ketoprofen had significant (P < 0.001) reduction of pyrexia from 0.5 to 5.0 hours after dosing. At 200 mg/kg, MSM has led to the opioid-like effect of hypothermia, possibly due to its synergistic effect with other compounds such as 7-hydroxymitragynine or mitragynine pseudoindoxyl. This article discusses concerns pertaining to toxicity of mitragynine and MSM, and possible involvement of cyclooxygenase and microsomal prostaglandin E2 synthase pathways. In conclusion, mitragynine and MSM possess dose-dependent antipyretic properties in mice

Experimental study on energy absorption of foam filled kraft paper honeycomb subjected to quasi-static uniform compression loading

A statistical analysis was performed first to evaluate the effect of factor and to obtain the optimum configuration of Kraft paper honeycomb. The factors considered in this study include density of paper, thickness of paper and cell size of honeycomb. Based on the three level factorial design,two-factor interaction model (2FI) was developed to correlate the factors with specific energy absorption and specific compression strength. From the analysis of variance (ANOVA), the most influential factor on responses and the optimum configuration was identified. Then, Kraft paper honeycomb with optimize configuration is used to fabricate foam-filled paper honeycomb with five different densities of polyurethane foam as filler (31.8, 32.7, 44.5, 45.7, 52 kg/m3). The foam-filled paper honeycomb are subjected to quasi-static compression loading. Failure mechanism of the foam filled honeycomb were identified, analyzed and compared with the unfilled paper honeycomb. The peak force and energy absorption capability of foam filled paper honeycomb are increases up to 32% and 30% compared to the summation of individual components

Effect of short-term ingestion of the methanolic extract of mitragyna speciosa on sperm quality in mice

Mitragyna speciosa (MS) which is known as “Ketum” in Malaysia and “Kratom” in Thailand is a tropical plant indigenous to Southeast Asia. The leaves of MS have been used by natives of these countries for their opium-like effects and cocaine-like stimulant activities to overcome fatigue, enhance tolerance to hard work, prolong the duration of sexual intercouse and increase libido in males. However, no scientific studies have been carries out to assess the effects of MS consumption on the quality of sperm in animals or man. In this study, the effect of short-term ingestion of MS on the quality of sperm in mice was investigated. Forty mice were divided into 5 groups; 2 controls and 3 treatments. The negative control group received 0.9% sodium chloride (NaC1, 10 mL/ kg) while the positive control received clomiphene (25 mg/70 kg). the respective treatment groups received either 50, 100 and 200 mg/kg of MS extract. The drugs and extracts were administered orally once daily for 14. The results showed an increase in the number of sperms in groups treated with MS. The morbidity rates of the sperm in groups treated with MS were markedly lower than that of the control groups. In addition, marked deformity in the sperm in the form of swelling at the tail was observed in the groups treated with MS. In conclusion, mice treated with MS showed an increase in the number of sperm count in spite of defect in sperm morphology and reduced sperm motility

Gallocatechin-silver nanoparticles embedded in cotton gauze patches accelerated wound healing in diabetic rats by promoting proliferation and inhibiting apoptosis through the Wnt/β-catenin signaling pathway

Background: Diabetes mellitus is a chronic metabolic disorder characterized by elevated plasma glucose levels. It is often defined as a lifestyle disease having severe economic and physiological repercussions on the individual. One of the most prevalent clinical consequences of diabetes is the lagging pace of injury healing leading to chronic wounds, which still to date have limited treatment options. The objective of this research is to look into the wound healing capabilities of gallocatechin (GC) and silver nanoparticles (AgNPs) impregnated patches in diabetic rats. Experimental rats were dressed patches and the wound healing skin region was dissected at the end of the experiment for molecular analysis. The wound healing rate in diabetic rats dressed with CGP2 and CGP3 & silver sulfadiazine (AgS) patches were found to be high. While mRNA and immunofluorescence or immunohistochemistry assays reveal that Wnt3a and β-catenin levels were higher with Gsk-3β and c-fos levels were lower in diabetic rats dressed with in CGP2 and CGP3 as compared with diabetic rats dressed with DC+CGP1. Furthermore, apoptosis markers such as caspase-3, caspase-9, and Bax levels were reduced, whereas anti-apoptosis maker (Bcl-2) and proliferation marker (PCNA) levels were increased in diabetic rats dressed with CGP2 and CGP3 as compared with diabetic rats dressed with DC+CGP1. In conclusion, the results demonstrated that GC-AgNPs-CGP (CGP2 & CGP3) dressing on diabetes wound rats decreased changes in Wnt3a/β-catenin pathways, resulting in lower apoptosis and greater proliferation, so drastically improving diabetic wound healing

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Enlightening Science: Addressing the Cognitive and Non-Cognitive Aspects of Science Learning

Physical science (or physics) is known to be one of the least popular school curriculum domains, mainly because of its complexity. When students encounter seemingly insurmountable difficulties when learning something, they lose the motivation to continue. It has been suggested that both the cognitive (e.g., students’ conceptual understanding and achievement) and non-cognitive (e.g., psychological aspects such as academic self-concept and motivation) factors of learning are essential for helping students achieve their optimal best in a curriculum domain. However, there has not been much research, if any, which uses a dual approach to investigate both aspects of science learning. Most research focused on either the cognitive or non-cognitive aspect. Research on cognitive aspects of learning suggests that element interactivity is a useful construct with which to examine students’ cognitive processes and the complexity of learning materials. However, there has been no illustration on how an analysis of interacting elements in science learning tasks may improve learning. Studies on the effects of reducing element interactivity on students’ achievement and motivation are also scarce. Research on non-cognitive aspects of learning suggests that motivation is necessary to sustain students’ engagement in learning. However, if the complexity of learning tasks is so high that students experience repeated failures, their motivation is not sustained. Therefore, both cognitive and non-cognitive factors play a crucial role in students’ learning and both must be present to ensure an optimal learning environment. The overarching aim of this thesis is to investigate the cognitive (i.e., students’ achievement and cognitive processes in terms of element interactivity) and non-cognitive aspects (i.e., self-concept and other motivational factors) of students’ learning of science. The thesis includes five studies. The first study showed that the five main findings from past self-concept research were applicable to the Grade 7 students from Singapore selected for the study. Students’ sense of competence in a curriculum domain enhanced their future achievement in that domain only, except for physics and math, which showed interrelatedness (i.e., the enhancement was transferable from one domain to the other). The findings showed a strong interplay between academic self-concept and achievement and highlighted the important role that academic self-concept plays in determining students’ learning outcomes. Therefore, strategies to enhance students’ self-concept should be implemented in schools. The results of the second study showed strong positive correlations between students’ achievement and their motivation within a school year. Students’ Grade 6 (final primary school year) achievement did not strongly contribute to their motivation in Grade 7, indicating the importance of providing an optimal learning environment in Grade 7 for a positive start to their secondary school education. The third study showed how the interactions between the elements (i.e., element interactivity) in problem solving tasks reflect their level of complexity and how the number of operational lines that students used to solve problems could indicate their level of expertise in problem solving in that domain. This study highlighted the role of element interactivity as a planning tool for learning tasks and how teachers may use it to gain insights into students’ cognitive processes. The fourth study involved an intervention, which reduced element interactivity during science instruction, and the results revealed that students’ achievement improved, and their science self-concept was maintained. The results and implications of the first four studies were used to design a dual-approach instruction to facilitate both cognitive and non-cognitive aspects of students’ learning in the fifth and final study. The results of the final intervention study indicated that the dual-approach instruction was beneficial. The experimental group of students outperformed the comparison group in both cognitive and non-cognitive factors. Results from multiple regression analyses revealed that those who experienced the intervention not only had higher achievement than those in the comparison group in the complex problem tasks, but also had higher motivation (i.e., self-regulation, task goal, inquiry, and educational and career aspirations) and higher academic self-concept (i.e., sense of competence). This thesis demonstrates that there are strong associations and a significant interplay between students’ achievement and motivation levels (i.e., cognitive and non-cognitive aspects of learning). The analysis of learning tasks and instruction in terms of element interactivity enables the scaffolding of complex learning tasks to suit students’ cognitive levels, leading to higher achievement. Higher achievement contributes to higher motivation levels, including students’ academic self-concept. When learning environments attend to basic psychological needs (i.e., a sense of competence, autonomy, and relatedness), students’ motivation is enhanced and when motivated students experience learning that is within their ability and cognitive load capacities, their self-beliefs and motivation in the learning domain are sustained. Attention to both cognitive and non-cognitive factors in learning situations maximizes students’ learning potential and should therefore be strongly considered by educators and curriculum planners