Blended Learning and Project Based Learning: The Method to Improve Students’ Higher Order Thinking Skill (HOTS)

The background of this research was the demands of the industrial revolution 4.0 era. Hence, the students should have high-oder thinking skills and lecturers must be able to create learning that was able to achieve these demands. This study examined the effect of Blended Learning and Project Based Learning in improving the students’ Higher Order Thinking Skill (HOTS). This research was an experimental research with a quasi-experiment design type. The sample of this research was 90 students from Primary School Teacher Education Department at State University of Padang. This research proven that the obtained t count = 4.374 with df = 392.24 and sig (1 way) = 0.000 where sig (1 way) <0.05. It concluded that there was an improving of students’ HOTS ability that learned using Blended Learning and Project Based Learning rather than of using Blended Learning only. This research of using Blende-Learning and Project Based learning could improve on students' higher-order thinking skills. This research implied using Blended Learning and Project Based learning model was an alternative to improve Higher Order Thinking Skill (HOTS). Keywords:  Blended Learning, Higher Order Thinking Skill (HOTS), Project Based Learning

Fairy Tale as a Medium for Children’s Character Cooperation Building

A fairy tale is a fantasy story which gives moral education, and can be one of the media used for character building. One of the values found in a fairy tale is cooperation. Children’s character building strategy is done through giving fairy tales, listening to fairy tales, and creating a supportive reading environment. This study aimed at observing the ability of children in identifying the character values found in fairy tales and their ability to implement the values in their daily life. The respondents of this study were 3-4-year-old students of PAUD Pelangi Palembang. The number of the respondents was 15 students. The study used mixed methods. The data were collected through interview, observation and test. The results revealed that the value of cooperation could be effectively implemented through fairy tales. Before they were told fairy tales, the students were reluctant to tidy up their toys after they finished playing together, but after they were given a fairy tale about cooperation, the children enthusiastically cooperated to tidy up their toys, tidy up the class’ benches, throw garbage and tidy up the books on the shelf

The effectiveness of learning to read and write arabic letters in early children at Taman Pendidikan Quran (TPQ)

The purpose of this study is to describe process of learning to read and write Arabic letters in early childhood at Taman Pendidikan Quran (TPQ) Nurul Muttaqin 4, the students' interest in learning, positive impacts or benefits for students, opportunities in learning, and challenges faced during learning. The research method used is qualitative with the subject of early childhood aged 4-8 years at TPQ Nurul Muttaqin 4. Data collection techniques by observing the teaching and learning process of students and interviews with one of the teachers and students concerned. The research results obtained include: 1. The process of learning to read and write Arabic letters for early childhood at TPQ Nurul Muttaqin 4 using the iqro' method for reading and writing 2. The students' interest in learning is very large in learning because the parents of the students support it. and very open so that students are very interested in this learning. 3. The positive impact or benefits obtained by the students vary after participating in learning using the iqro' method, because each child has a different level of ability. There are children who are proficient in reading but lacking in writing Arabic letters. Vice versa. 4. The opportunities for learning are very good because the surrounding community is supportive and open with evidence that their children are entrusted to study at this TPQ. 5. The challenge faced during learning is the feeling of drowsiness that comes to students during learning, which makes it difficult for students to concentrate. The solution that can be done is that teachers can make learning as interesting as possible so that it makes students enthusiastic and interested in learnin

Identification of sulfation sites of metabolites and prediction of the compounds’ biological effects

Characterizing the biological effects of metabolic transformations (or biotransformation) is one of the key steps in developing safe and effective pharmaceuticals. Sulfate conjugation, one of the major phase II biotransformations, is the focus of this study. While this biotransformation typically facilitates excretion of metabolites by making the compounds more water soluble, sulfation may also lead to bioactivation, producing carcinogenic products. The end result, excretion or bioactivation, depends on the structural features of the sulfation sites, so obtaining the structure of the sulfated metabolites is critically important. We describe herein a very simple, high-throughput procedure for using mass spectrometry to identify the structure—and thus the biological fate—of sulfated metabolites. We have chemically synthesized and analyzed libraries of compounds representing all the biologically relevant types of sulfation products, and using the mass spectral data, the structural features present in these analytes can be reliably determined, with a 97% success rate. This work represents the first example of a high-throughput analysis that can identify the structure of sulfated metabolites and predict their biological effects

Computational design of syntheses leading to compound libraries or isotopically labelled targets

Although computer programs for retrosynthetic planning have shown improved and in some cases quite satisfactory performance in designing routes leading to specific, individual targets, no algorithms capable of planning syntheses of entire target libraries - important in modern drug discovery - have yet been reported. This study describes how network-search routines underlying existing retrosynthetic programs can be adapted and extended to multi-target design operating on one common search graph, benefitting from the use of common intermediates and reducing the overall synthetic cost. Implementation in the Chematica platform illustrates the usefulness of such algorithms in the syntheses of either (i) all members of a user-defined library, or (ii) the most synthetically accessible members of this library. In the latter case, algorithms are also readily adapted to the identification of the most facile syntheses of isotopically labelled targets. These examples are industrially relevant in the context of hitto-lead optimization and syntheses of isotopomers of various bioactive molecules

Application of in vitro Drug Metabolism Studies in Chemical Structure Optimization for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)

Currently no approved treatment exists for fibrodysplasia ossificans progressiva (FOP) patients, and disease progression results in severe restriction of joint function and premature mortality. LDN-193189 has been demonstrated to be efficacious in a mouse FOP disease model after oral administration. To support species selection for drug safety evaluation and to guide structure optimization for back-up compounds, in vitro metabolism of LDN-193189 was investigated in liver microsome and cytosol fractions of mouse, rat, dog, rabbit, monkey and human. Metabolism studies included analysis of reactive intermediate formation using glutathione and potassium cyanide (KCN) and analysis of non-P450 mediated metabolites in cytosol fractions of various species. Metabolite profiles and metabolic soft spots of LDN-193189 were elucidated using LC/UV and mass spectral techniques. The in vitro metabolism of LDN-193189 was significantly dependent on aldehyde oxidase, with formation of the major NIH-Q55 metabolite. The piperazinyl moiety of LDN-193189 was liable to NADPH-dependent metabolism which generated reactive iminium intermediates, as confirmed through KCN trapping experiments, and aniline metabolites (M337 and M380), which brought up potential drug safety concerns. Subsequently, strategies were employed to avoid metabolic liabilities leading to the synthesis of Compounds 1, 2, and 3. This study demonstrated the importance of metabolite identification for the discovery of novel and safe drug candidates for the treatment of FOP and helped medicinal chemists steer away from potential metabolic liabilities

Pharmacogenetic & Pharmacokinetic Biomarker for Efavirenz Based ARV and Rifampicin Based Anti-TB Drug Induced Liver Injury in TB-HIV Infected Patients

BACKGROUND: Implication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury (DILI) has not been yet studied. We performed a prospective case-control association study to identify the incidence, pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury (DILI) in HIV and tuberculosis (TB) co-infected patients. METHODS AND FINDINGS: Newly diagnosed treatment naïve TB-HIV co-infected patients (n = 353) were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy, and assessed clinically and biochemically for DILI up to 56 weeks. Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 genes were done. The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant association of DILI with being of the female sex (p = 0.001), higher plasma efavirenz level (p = 0.009), efavirenz/8-hydroxyefavirenz ratio (p = 0.036), baseline AST (p = 0.022), ALT (p = 0.014), lower hemoglobin (p = 0.008), and serum albumin (p = 0.007), NAT2 slow-acetylator genotype (p = 0.039) and ABCB1 3435TT genotype (p = 0.001). CONCLUSION: We report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients. Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients. Close monitoring of plasma efavirenz level and liver enzymes during early therapy and/or genotyping practice in HIV clinics is recommended for early identification of patients at risk of DILI

Dose adjustment of the non-nucleoside reverse transcriptase inhibitors during concurrent rifampicin-containing tuberculosis therapy: one size does not fit all

Importance of the field: HIV/tuberculosis (TB) co-infection is common and associated with high mortality. Simultaneous highly active antiretroviral therapy during TB treatment is associated with substantial survival benefit but drug–drug interactions complicate NNRTI dosing. Areas covered in this review: We reviewed the impact of rifampicin-containing TB therapy on the NNRTIs pharmacokinetics and clinical outcome. PubMed database was searched from 1966 to July 2009 using the terms efavirenz, rifampicin, nevirapine, pharmacokinetics, pharmacogenetics, HIV, TB, CYP2B6, CYP3A4 and metabolism. References from identified articles and abstracts from meetings were also reviewed. What the reader will gain: A comprehensive review of the literature on this subject including pharmacokinetic and clinical studies. Most studies were small, observational or underpowered to detect the true effect of rifampicin on NNRTI-based therapy. None of the studies were controlled for genetic factors and there were limited data on children. Take home message: There were insufficient data to make definitive recommendations about dose adjustment of the NNRTIs during rifampin-containing therapy. Current data suggest that the standard dose of efavirenz or nevirapine is adequate in most HIV/TB co-infected adults. However, more research is needed in pediatric populations as well as to define role of drug–gene interactions