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Background: Spleen plays a role in human immune system as well as in recycling and filtering blood. The aging spleen is associated with fibrosis and impaired immune system, increasing individual vulnerability to getting infections. Regular physical activity is essential to maintain and enhance body fitness, endurance, and immune system.Objective: This study aimed to investigate the effects of mild and moderate-intensity treadmill exercise on the aging spleen by examining fibrosis and the number of macrophages in d-Galactose-induced aging rat models.Methods: Twenty-four male Wistar rats were randomly divided into four groups: G1 (control group), G2 (d‐Galactose, no exercise), G3 (d‐Galactose, low-intensity exercise), and G4 (d‐Galactose, moderate-intensity exercise). d-Galactose was administered intraperitoneally on day 0 and treadmill exercise was given for four weeks following the modified Brown et al. (2007) protocol. Spleens were histologically processed and stained for picrosirius red and against CD68+ antibody. Percentage of fibrosis fraction area and macrophage cell count were obtained using ImageJ, and the data were analyzed statistically using SPSS software.Results: The aging spleen did not show any differences in weight, length, and width among groups (P > 0.05). The administration of d-Galactose in rats causes fibrosis and an increased number of macrophages. Low and moderate-intensity treadmill exercise could not lower the percentages of fibrosis fraction area. However, the moderate-intensity treadmill exercise was effective in lowering macrophage number.Conclusion: Moderate-intensity treadmill exercise was effective in lowering macrophage cell count in the aging rat spleen induced by d-Galactose.

BACKGROUND: Inflammatory Bowel Disease (IBD) causes gastrointestinal tract dysregulation and triggers inflammation. Severe inflammatory events often lead to leukocyte infiltration. Yacon is known to have anti-inflammatory properties, making it a potential alternative treatment for colitis. AIMS: To investigate colonic Interleukin-23 (IL-23) level and leukocyte infiltration profile in 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)-induced colitis mouse model treated with yacon syrup powder. METHODS: Thirty male BALB/c mice (5 weeks old, body weight: 30.02±1.28 g) were randomly divided into 6 groups (K1-K6). Intra-rectal administration of TNBS was performed to K2-K6 to make the colitis model. K4-K6 were given yacon syrup powder daily for 14 days with the dose of 0.165, 0.331, and 0.662 g/30 g body weight (BW) respectively. IL-23 levels of colonic tissue were measured using ELISA. Leukocyte infiltration profile was calculated through microscopic observation of histology slides and presented in percentage and degree. RESULTS: Significantly different IL-23 levels were observed among the groups (P

The Covid-19 pandemic worsened the physical inactivity pandemic and also increased sedentary behavior across the population, including university students. While physical inactivity and sedentary behavior are detrimental to health and academic performance, there is an urgent need to help university students to adopt an active lifestyle during post-pandemic life. This narrative review discussed current physical activity (PA) and sedentary behavior recommendations, practical tips for adopting an active lifestyle by applying PA doses using the frequency, intensity, time, and type (FITT) principle, and behavioral strategies to adopt and maintain an active lifestyle. Finally, several considerations related to the PA-related musculoskeletal injury and cardiovascular events risks were also discussed with examples from interventions during the pandemic in university settings.

Introduction: Chlorogenic Acid (CGA) is an antifibrotic and antioxidant for fibrotic tissues. These double roles be able to inhibit or fibrotic tissues chains because of internal and external issues. For example, virus, bacteria or other pathogens and also by drugs, alcohol, cigarettes, etc. as external factor that affect quality of body tissues. Toll-Like Receptor-4 (TLR-4) as a marker fibrotic tissues. It is a key for researcher could be find out by expression performance. The aim of this study is to reveal the CGA as a candidate of antifibrotic & antioxidant in liver fibrosis that induced by CCL4. Methods: This is a pure experimental research with a simple experimental design or post-test only control group design. The total 29 mices of 2.5-month-old male Swiss mices with weigh 35-40 gram divided into 6 group: 3 groups of controls (injected by natrium chloride, CGA, and CCL4) and 3 groups of treated (injected by CGA doses 42 mg/kg, 63 mg/kg or 84 mg/kg). Liver organ was used to examine the expression of TLR-4 by rt-PCR. This research revealed that expression of TLR-4 lower than the CCL4 control group (respectively, p=0.042; p=0.005; p=0.006; and p=0.001). Higher dose of CGA showed greater ability as anti-fibrotic through inhibit the expression of TLR-4. Some research found the expression of TLR-4 has been decreased by treatment of Clorogenic Acid (CGA). Conclusion: To sum up, CGA has double roles to repair liver fibrotic tissues. The greater doses of CGA, the stronger inhibition of TLR-4 expression.

Pulmonary arterial hypertension (PAH) is a debilitating disease that results from progressive remodeling and inflammation of pulmonary arteries. PAH develops gradually, is difficult to diagnose, and has a high mortality rate. Although mutation in the bone morphogenetic protein receptor 2 (BMPR2) gene has been identified as the main genetic cause of PAH, the underlying pathways involving the pathophysiology of PAH are complex and still not fully understood. Endothelial dysfunction has been observed in PAH development that results in a multitude of disturbances in the cellular processes in pulmonary vessels. Changes in the pulmonary vasculature caused by the disruption of BMPR2 signaling are observed in three main vascular components; endothelial cells, smooth muscle cells, and fibroblasts. BMPR2 also has a prominent role in maintenance of the immune system. The disruption of BMPR2 signaling pathway causes an increased degree of inflammation and decreases the ability of the immune system to resolve it. Inflammatory processes and changes in pulmonary vasculature interact with one another, resulting in the progression of chronic PAH. In this review, we highlight the various components of vascular remodeling and immune response that are caused by disruption of BMPR2 signaling, including the clinical evidence and the prospects of these components as a potential target for PAH therapy. Indeed, development of drugs to target the pathogenic pathways involved in PAH may complement existing treatment regimens and improve patient prognosis.

Background: During the COVID-19 pandemic, there were reductions in university students' physical activity, which further increased their mental distress, calling for technology-based physical activity interventions to address the challenges in delivering in-person interventions. This study aimed to develop a technology-based physical activity intervention and pilot test it.Methods: We developed a virtually-delivered team-based physical activity challenge using the Behavior Change Wheel and Co-creation Framework based on Self-determination Theory. A pilot study was conducted in the evaluation phase to measure the recruitment rate, dropout rate, change in physical activity and mental distress, while identifying problems and collecting participants' opinions regarding the challenge. Wilcoxon signed-rank tests were conducted to assess the change in physical activity and mental distress. Qualitative data were analyzed using thematic analysis.Results: A three-week physical activity challenge comprising five identified intervention functions was held with 480 participants. The recruitment rate was 84.8% resulting from 407 virtual challenge participants who were conveniently joined as research participants. The dropout rate for the pilot study was 10.96% resulting from the incompatibility problems with the application. Among sample participants who lacked physical activity, participation in this challenge improved their physical activity by 52.5 minutes of moderate-intensity physical activity per week and reduced their mental distress by 3 points of self-reporting questionnaire-20 score. Issues regarding the virtual application, the influence of participation in the challenge on basic psychological needs, and lack of time were identified as the main barriers to physical activity from participants' opinions.Conclusion: A co-created physical activity intervention developed using the Behavioral Change Wheel Framework inspired high interest from university students and may increase their physical activity and improve their mental health. Several suggestions were discussed to address the identified problems and improve the internal and external validity of the evaluation phase.Trial registration: TCTR20220720004 (retrospectively registered on 19/07/2022)

Genetic factors are involved in the development, progression, and severity of non-alcoholic fatty liver disease (NAFLD). Polymorphisms in genes regulating liver functions may increase liver susceptibility to NAFLD. Therefore, we conducted this literature study to present recent findings on NAFLD-associated polymorphisms from published articles in PubMed from 2016 to 2021. From 69 selected research articles, 20 genes and 34 SNPs were reported to be associated with NAFLD. These mutated genes affect NAFLD by promoting liver steatosis (PNPLA3, MBOAT7, TM2SF6, PTPRD, FNDC5, IL-1B, PPARGC1A, UCP2, TCF7L2, SAMM50, IL-6, AGTR1, and NNMT), inflammation (PNPLA3, TNF-α, AGTR1, IL-17A, IL-1B, PTPRD, and GATAD2A), and fibrosis (IL-1B, PNPLA3, MBOAT7, TCF7L2, GATAD2A, IL-6, NNMT, UCP, AGTR1, and TM2SF6). The identification of these genetic factors helps to better understand the pathogenesis pathways of NAFLD.

An immune system recognizes and responds to antigens entering the body. Maintaining these roles, components of the immune system need energy obtained from nutrients such as carbohydrates, proteins, and lipids. This study reviews and discusses roles of lipids, particularly fatty acids, in regulations of the immune system. This study was conducted by conducting a literature study on published research articles written in English. The articles were obtained from PubMed and Google Scholar by using search keywords: lipid, fatty acids, immune, regulation, inflammation, and response. Lipids are a group of biomolecule compounds composed of carbon, oxygen, and hydrogen, and they are classified into simple, compound and complex lipids. Fatty acids are compound lipids that act as a main fuel for metabolism, an essential component for all membranes, and a gene regulator. Fatty acids have a modulating effect on immune cells, such as: acting as a host defence, activating the immune system, interacting with nuclear transcription factors, playing roles in inflammatory responses, promoting apoptosis, as well as influencing lymphocyte proliferation, cytokine production, and Natural Killer (NK) cell activities. However, the modulation of the immune system by lipids is influenced by various factors such as concentration and types of fatty acids, types of immune cells, and species. This study is suggested to provide an overview of beneficial roles of lipids in maintaining immunity., Not just as energy source, lipids also have an important role in body defense mechanism by affecting the components of immune system. Recent study shows that lipid action in signal transduction processes of immune system affects the proliferation, migration, and apoptosis of immune cells. Different types of lipids elicit different functions so it is necessary to understand which types of lipids that affect the immune system and how lipids regulate the immune system. This review highlights the importance of lipid action in maintaining our health, preventing inflammation, inhibiting the actions of tumor cells, and as a treatment of diseases.

Background Inflammatory bowel disease is a chronic inflammatory condition associated with damage to the intestinal mucosal barrier. Supplementation of yacon tubers has been known to have positive effect on intestinal health. Therefore, we conducted the present study to investigate the effect of yacon tuber powder on Th1 activation pathway by evaluating IFN-γ levels and the number of goblet cells in the colon of colitis mouse models. Methods Thirty BALB/c mice were divided into five groups: 1, control group (G1) and 2-5, TNBS-induced colitis groups (GII-GV). Yacon powder was given to three of the TNBS-induced colitis groups with the doses of 0.165 g/30 g BW (GIII), 0.331 g/30 g body weight (BW; GIV), and 0.662 g/30 g BW (GV) for 14 days. IFN-γ levels were assessed using ELISA, while number of goblet cells was calculated based on histological observation. Results Significantly lower IFN-γ levels was observed in GV compared to colitis group (GII) (p = 0.007). GV also showed significantly higher number of goblet cells per 100 epithelial cells in 20 crypts (p = 0.000) than GII. Conclusion The administration of yacon powder at a dose of 0.662 g/30 g BW could decrease IFN-γ levels and improve the healing of intestinal mucosa in colitis mouse models by increasing the number of goblet cells.

A new disease caused by a newly-found coronavirus, known as Coronavirus Disease 2019 (COVID-19), has been declared as a pandemic by World Health Organization (WHO). This new disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak started in late December of 2019 and it did not take a long time until it spread to more than 200 countries in the world with over 4 million confirmed cases to date. The number keeps skyrocketing as day passes, followed by the increasing number of fatalities. Among all of the infected patients, elderly is one of the vulnerable populations. Studies reported that the risk of infection is doubled in older people. This infection-susceptible characteristic may be due to the weak immune system, therefore they lack the capabilities to fight the infection. The deterioration of immune system in elderly is known as immunosenescence. The aim of this literature review is to understand the effect of immunosenescence in the immunopathogenesis and susceptibility of elderly who are exposed to COVID-19 infection. (J Respir Indo. 2020; 40(3): 182-91)

Background : Low fitness is an emerging factor for cardiovascular diseases. Physical activity and sitting time are arising factors that influence fitness level. There are some debates on what domain of physical activity and sitting time that have more influences on fitness level. The aims of this study were to (1) explore each domain of physical activity & sitting time and analyze their associations with low fitness in male working adults and (2) explore the differences between sitting time on a working day and a day-off. Method :In this cross-sectional study, a total of 31 healthy male staffs were recruited. Participants used International Physical Activity Questionnaire (IPAQ) long version to recall their physical activity and sitting time, and their fitness level was measured by a submaximal exercise test. Data were analyzed both by univariate and multivariate techniques. Multivariable logistic regressions were employed to calculate Odds Ratio (OR) of low fitness by each domain of physical activity and sitting time. Result : Data of 27 participants were considered for analysis. Total physical activity was inversely associated with low fitness [OR 0.961, 95% Confidence Interval (95% CI) 0.928 – 0.995]. Total sitting time and sitting time on a working day were positively associated with low fitness (total sitting time: OR 1.101, 95% CI 1.001-1.211; sitting time on a working day: OR 1.01, 95% CI 1.001-1.019). We also observed that sitting on a working day was significantly higher than sitting time on a day-off (p = 0.004). Conclusion : The results support association of total physical activity, total sitting time and sitting time on a working day with fitness level. There were also difference between sitting time on a working day and a day-off. Bangladesh Journal of Medical Science Vol.18(2) 2019 p.279-287

Introduction: World Health Organization (WHO) recommends exclusive breastfeeding for new-borns until 6 months of age. However, exclusive breastfeeding in Indonesia only reached 52.3% in 2014 and 65.16% in 2018. It is known that administration of infant formula and non-formula supplements to infants aged less than 6 months increases the risk of Acute Respiratory Infections (ARIs). In addition, the high prevalence of ARIs in infants in Sleman Regency, Indonesia indicates the need of optimal early prevention. Therefore, we conducted this study to confirm that mothers’ knowledge of breastfeeding and infant feeding types affect the prevalence of Acute Respiratory Infections (ARIs). Methods: Data were collected through questionnaires from 50 mothers with infants aged 7-12 months who had experienced ARIs in the last 3 months (case group) and 50 mothers with healthy infants (control group). Collected data were then analysed using Chi-Square, Logistic Regression, Lambda, and Somers’ D tests. Results: The results showed that types of infant feeding are associated with the prevalence of ARIs. Non-breastfed infants were 14 times riskier to contract ARIs. Mothers’ knowledge of exclusive breastfeeding influence their preferences of feeding practice. However, their attitude towards breastfeeding did not appear to significantly affect their choices of feeding practice. Conclusion: Exclusive breastfeeding during the first 6 months of an infant’s life can lower the prevalence of ARIs for when they are older. Mothers’ good knowledge of breastfeeding is associated with its practice., Journal of Preventive Medicine and Hygiene, Vol. 61 No. 3 (2020): 2020613

Background: Self-efficacy is the ability to organize or carry out an action in achieving goals. Adolescence is a vulnerable period, since in this phase adolescents are in the genital phase and their sexual urge reaches its peak. Sexual and reproductive health self-efficacy is a person's belief in making decisions regarding his or her sexuality. Education plays important role in adolescents regarding their decision regarding sexual and reproductive health. Therefore, it is necessary to conduct research on the effect of AViRSex Education toward adolescent’s sexual and reproduction health self-efficacy.Objective: To find out the effect of AViRSex (Aid Video for Reproduction and Sexuality) Education toward adolescent’s sexual and reproduction health self-efficacy.Methods: This was quantitative research with quasi-experiment design which was conducted in November-Desember 2019 and took 122 students from SMP N 1 Ngemplak and SMP N 2 Ngemplak Sleman as research subjects. This research used the adolescent sexual and reproduction health self-efficacy questionnaire with validity score 0,97 and reliability score 0,74. Data was analyzed using Paired t-test, Mann-Whitney, Pearson Product Moment, and Eta Test.Result: There was a significant change in the pretest and post-test score of the intervention group (p= 0,008) while there was not any significant change in the pretest and post-test score of the control group (p= 0,367). There was not any significant difference between the pretest and post-test score of the control and intervention groups (p= 0,067). There was no relationship between self-efficacy with age (r= -0,039) and sexual reproductive health experiences (Fcount = 2,062). There was a relationship between sex with self-efficacy (Fcount = 6,28).Conclusion: AViRSex Education could increase sexual and reproduction health self-efficacy score on 12-14 years old adolescent.Keywords: adolescent; self-efficacy; sexual and reproduction health ABSTRAKLatar belakang: Efikasi diri merupakan kemampuan untuk mengatur atau melaksanakan suatu tindakan dalam mencapai tujuan. Masa remaja merupakan masa rentan, dimana remaja berada fase genital dan dorongan seksual yang mencapai fase puncak. Efikasi diri kesehatan seksual dan reproduksi merupakan keyakinan seseorang dalam memutuskan terkait dengan seksualitasnya. Edukasi berperan penting dalam membuat keputusan terkait kesehatan seksual dan reproduksinya. Oleh karena itu, perlu dilakukan penelitian mengenai pengaruh Edukasi AViRSex terhadap efikasi diri terkait kesehatan seksual dan reproduksi pada remaja.Tujuan: Untuk mengetahui pengaruh Edukasi AVirSex (Aid Video for Reproduction and Sexuality) terhadap efikasi diri terkait kesehatan seksual dan reproduksi pada remaja.Metode: Penelitian ini merupakan penelitian kuantitatif dengan rancangan quasi-experimental. Penelitian dilaksanakan pada November – Desember 2019 dengan jumlah subjek sebanyak 122 siswa dari SMPN 1 dan SMPN 2 Ngemplak, Sleman. Instrumen yang digunakan adalah kuesioner efikasi diri kesehatan seksual dan reproduksi, dengan hasil validitas 0,97 dan reliabilitas 0,74. Analisis data yang digunakan yaitu Paired t-test, Mann-Whitney, Uji Pearson, dan Uji Eta.Hasil: Analisis data menunjukan adanya perubahan signifikan pada skor pre-test dan post-test kelompok intervensi (p= 0,008) dan tidak ada perubahan signifikan pada skor pre-test dan post-test kelompok kontrol (p= 0,367). Tidak ada perbedaan signifikan selisih skor efikasi diri pre-test dan post-test kelompok kontrol dan intervensi (p= 0,067). Tidak ada hubungan antara efikasi diri dengan usia (r= -0,039) dan pengalaman kesehatan seksual reproduksi (Fhitung= 2,062). Ada hubungan jenis kelamin dengan efikasi diri (Fhitung=6,28).Kesimpulan: AViRSex dapat meningkatkan skor efikasi diri kesehatan seksual dan reproduksi pada remaja usia 12 – 14 tahun.Kata Kunci: efikasi diri; kesehatan seksual dan reproduksi; remaja

Background: Professionalism is a skills area that should be mastered by medical graduates. The period of formal education is essential for the formation of professionalism. The involvement of internal factors, such as academic motivation, and external factors, such as the learning environment, might play a role in the development and learning of professional identity. Aim: To determine the profiles of academic motivation and its relationship between student professional identity during their degree courses. Methods: This cross-sectional study included 531 medical students in the early, mid, and late phases of their courses in the Gadjah Mada University Faculty of Medicine. The Academic Motivation Scale of Vallerand was used to assess academic motivation, and the Professional Identity Scale of Adams to assess professional identity. Results: The mean scores of academic motivation domains including intrinsic, extrinsic, and lack of motivation among medical students in the Gadjah Mada University Faculty of Medicine were 5.02 ± 0.87, 4.86 ± 0.88, and 1.83 ± 0.96 (mean ± standard deviation), respectively. No significant differences were found between the intrinsic and extrinsic motivation scores among students in the three phases of education, while the scores on lack of motivation among students in earlier phases were lower than students in the mid and late phases (P

Background A large-scale Japanese study showed that low skeletal muscle index (SMI) and intramuscular fat (IMF) deposition are associated with hepatocellular carcinoma (HCC) survival. Here, we evaluated the effects of SMI and IMF on the survival of Indonesian HCC patients, whose characteristics differ from those of Japanese patients. Methods SMI and mean muscle attenuation (MA) were evaluated using computed tomography images of the third lumbar vertebra (L3) in a prospective cohort of 100 Indonesian HCC patients. Clinical, laboratory and body composition data were analysed using the Kaplan–Meier method and Cox regression model to investigate which factors are associated with prognosis. Results Of 100 patients, 31 were diagnosed with sarcopenia (L3 SMI value ≤36.2 cm2/m2 for men and ≤ 29.6 cm2/m2 for women), and 65 had IMF deposition (MA value ≤44.4 HU for men and ≤ 39.3 HU for women). These groups had shorter median survival than the reference groups (both P P = 0.016), IMF deposition (HR, 3.580; P P P P = 0.020), and male gender (HR: 3.211, P Conclusion Sarcopenia and IMF deposition showed superior value in combination with BCLC stage and JIS score for predicting the survival of Indonesian HCC patients. Increased awareness and strategies to prevent or reverse these factors might improve patient outcomes. (Electric word counts: 249).

Aging increases liver susceptibility to diseases and it causes inflammation in liver tissue which can lead to fibrosis. Studies suggest that aging is caused by the accumulation of free radicals. Lack of physical activity can lower hormone levels and increase free radicals that can accelerate the aging process. Hence, physical activity is very important to maintain functions of organs. This research was aimed to study the effects of low and moderate treadmill exercise on d‐Galactose‐exposed aging rat model by evaluating the degree of hepatic fibrosis, number of M1 and M2, and M1/M2 ratio. Twenty‐four 3‐month‐old male Wistar aging model rats were randomly divided into four groups, that is, three treatment groups with daily 300 mg kgBW−1 d‐Galactose injection administrated intraperitoneally for 4 weeks and 1 control group with normal saline injection. Two of the d‐Galactose treated groups were given low and moderate treadmill exercise for 4 weeks. It was concluded that low intensity treadmill exercise significantly lowered the degree of d‐Galactose‐exposed hepatic fibrosis, and moderate treadmill exercise was able to restore the injured liver tissue back to the non‐aging state. Administration of d‐Galactose causes inflammation marked by the elevated number of M1 and M2 macrophages. Moderate treadmill exercise drove M1/M2 ratio back to the control condition., We investigated the potential hepatoprotective effects of treadmill exercise in d‐Galactose‐exposed ageing rat model. Administration of d‐Galactose caused liver fibrosis and inflammation marked by the elevated number of M1 and M2 macrophages. Low and moderate treadmill exercise could significantly lower the degree of hepatic fibrosis and restored the M1/M2 ratio back to the non‐aging state.

Background A large-scale Japanese retrospective study showed that low skeletal muscle index (SMI) and intramuscular fat (IMF) deposition are associated with hepatocellular carcinoma (HCC) survival. Here, we evaluated the effects of SMI and IMF on the survival of Indonesian HCC patients, whose characteristics differ from those of Japanese patients.Methods SMI and mean muscle attenuation (MA) were evaluated using computed tomography images of the third lumbar vertebra (L3) in a prospective cohort of 100 Indonesian HCC patients. Clinical, laboratory and body composition data were analysed using the Kaplan–Meier method and Cox regression model to investigate which factors are associated with prognosis.Results Of 100 patients, 31 were diagnosed with sarcopenia (L3 SMI value ≤36.2 cm 2 /m 2 for men and ≤29.6 cm 2 /m 2 for women), and 65 had IMF deposition (MA value ≤44.4 HU for men and ≤39.3 HU for women). These groups had shorter median survival than the reference groups (both P

The aim of this study was to identify the effects of Ocimum sanctum Linn. ethanolic extract (OSE) on the neurons of the CA1, CA3, and DG hippocampal areas with the use of in vivo and in vitro models of Alzheimer's diseases (AD). Twenty-one two-month-old male rats were divided into three groups: untreated (Group A, n = 3), AD rats model pretreated with OSE followed by induction for Trimethyltin (TMT) on day 7 (group B, n = 9), and AD rats model treated with OSE both as pre-TMT introduction for 7 days and post-TMT induction for 21 days (group C, n = 9). AD rats were sacrificed on days 7, 14, and 21, and brain samples were collected and analyzed for neuronal density and neuropeptide Y (NPY) immunoreactivity. To corroborate the in vivo observations, HEK-293 cells were treated with TMT and used as an in vitro model of AD. The results were then analyzed using FITC Annexin V and flow cytometry. Nuclear fragmentation was observed in cells stained with Hoechst 33342 by confocal microscopy. The results showed a significant increase in the number of neurons and NPY expression in the AD rats that were pre- and post-treated with OSE (p 0.05). Indeed, OSE was able to retain and promote neuronal density in the rat model of AD. Further studies of an in vitro model of neurodegeneration with Ocimum sanctum Linn. ethanolic extract inhibited apoptosis in TMT-induced HEK-293 cells. Moreover, OSE prevented nuclear fragmentation, which was confirmed by staining the nuclei of HEK-293 cells. Taken together, there findings suggest that OSE has the potential as a neuroprotective agent (retaining the autobiographical memory),and the neuroproliferation of neurons in the CA1, CA3, and DG hippocampal areas in the rats¡ model of neurodegeneration was mediated by activation of NPY expression.

Human leukocyte antigen (HLA) DPA1/DPB1 variants have been reported to influence Hepatitis B virus (HBV) infection. HLA-DPA1/DPB1 plays a pivotal role in antigen presentation to CD4(+) helper T cells and influences the outcome of HBV infection. To investigate the influence of HLA-DP variants on the outcome of HBV infection in an Indonesian population where it has the third-highest prevalence of HBV infection worldwide, we performed a case-control study of 686 participants, including patients with HBV-related advanced or nonadvanced liver disease, patients with spontaneously resolved HBV, and healthy controls. Single-nucleotide polymorphisms in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs228388) were genotyped using real-time TaqMan® genotyping assays. Because rs2281388 deviated from Hardy-Weinberg equilibrium, it was excluded from subsequent analyses. The results of logistic regression analyses showed that the HLA-DPB1 rs9277535 variants were associated with a reduced risk of persistent HBV infection (odds ratio [OR] 0.70, 95% confidence interval [95% CI] 0.52-0.96, P=0.026, additive genetic model; OR 0.60, 95% CI 0.38-0.96, P=0.033, dominant genetic model). The HLA-DPA1 rs3077 variant was associated with a protective effect increasing the spontaneously resolved HBV infection (OR 0.64, 95% CI 0.41-0.98, P=0.039, dominant genetic model). By contrast, the HLA-DPB1 rs3135021 variant was not associated with the outcome of HBV infection, including susceptibility, spontaneously resolved, or disease progression. Combinations of haplotype markers were also associated with HBV susceptibility (CA for rs3077-rs9277535, OR 0.57, 95% CI 0.36-0.92, P=0.021; GA for rs3135021-rs9277535, OR 0.56, 95% CI 0.36-0.86, P=0.0087). In conclusion, these findings confirm that HLA-DPA1/DPB1 variants were associated with the outcomes of HBV infection in an Indonesian population.

Quasispecies of hepatitis B virus (HBV) with variations in the major hydrophilic region (MHR) of the HBV surface antigen (HBsAg) can evolve during infection, allowing HBV to evade neutralizing antibodies. These escape variants may contribute to chronic infections. In this study, we looked for MHR variants in HBV quasispecies using ultradeep sequencing and evaluated the relationship between these variants and clinical manifestations in infected patients. We enrolled 30 Indonesian patients with hepatitis B infection (11 with chronic hepatitis and 19 with advanced liver disease). The most common subgenotype/subtype of HBV was B3/adw (97%). The HBsAg titer was lower in patients with advanced liver disease than that in patients with chronic hepatitis. The MHR variants were grouped based on the percentage of the viral population affected: major, ≥20% of the total population; intermediate, 5% to

Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome are an important factor in low therapeutic effectiveness. Nonetheless, the prevalence of these mutations in HBV strains isolated previously in Indonesia has not been systematically examined. Therefore, in this study, we investigated the profile of mutations in the RT region and the associations of these mutations with amino acid changes in the surface protein in the virus of treatment-naive Indonesian HBV carriers. Overall, 96 sequences of the full-length Indonesian HBV genomes (genotype B, n = 54; genotype C, n = 42) were retrieved from the National Center for Biotechnology Information. Naturally occurring primary and/or compensatory drug resistance mutations were found in 6/54 (11.1%) genotype B strains and in 1/42 (2.4%) genotype C strains. The potential mutations underlying resistance to a nucleos(t)ide analog and/or pretreatment mutations were more frequent in both genotypes but more frequent in genotype C strains than in genotype B strains. The A-B interdomain region in the RT gene was more frequently mutated in genotype C than in genotype B (3.51 ± 2.53 vs. 1.08 ± 1.52, P ＜ 0.001). Knowledge about the mutational profiles of the RT gene and changes in the surface protein may help clinicians to select the most appropriate antiviral drug and vaccination or HBV immunoglobulin regimen for management of HBV infection in Indonesia.

Ethical Clearance dr Widya 2014 (SECOND). (PDF 996Â kb)

A nucleos(t)ide analog (NA) is the common antiviral drug available for directly treating hepatitis B virus (HBV) infection. However, its application has led to the emergence of NA-resistant mutations mostly in a conserved region of the reverse transcriptase domain of HBV polymerase. Harboring NA-resistant mutations decreases drug effectiveness and increases the frequency of end-stage liver disease. The invention of next-generation sequencing that can generate thousands of sequences from viral complex mixtures provides opportunities to detect minor changes and early viral evolution under drug stress. The present study used ultra-deep sequencing to evaluate discrepant quasispecies in the reverse transcriptase domain of HBV including NA-resistant hotspots between seven treatment-naïve Indonesian patients infected with HBV and five at the early phase of treatment. The most common sub-genotype was HBV B3 (83.34%). The substitution rate of variants determined among amino acids with a ratio of ≥ 1% changes was higher among the population in conserved regions (23.19% vs. 4.59%, P = 0.001) and in the inter-reverse transcriptase domain (23.95% vs. 2.94%, P = 0.002) in treatment naïve, than in treated patients. Nine hotspots of antiviral resistance were identified in both groups, and the mean frequency of changes in all patients was < 1%. The known rtM204I mutation was the most frequent in both groups. The lower rate of variants in HBV quasispecies in patients undergoing treatment could be associated with virus elimination and the extinction of sensitive species by NA therapy. The present findings imply that HBV quasispecies dynamically change during treatment.

Background: One of scheduling problems in educational sector currently was the course scheduling in college or well known as University Course Timetabling Problem (UCTP). The UCTP was comprehensive because of the policy difference among the university, faculties, and departments. The Faculty of Medicine Universitas Gadjah Mada, which organizes a block system has a different and more complex scheduling type than other faculties with non-block system. The porpose of this research was to build a mathematic model of block system UCTP in Faculty of Medicine Universitas Gadjah Mada to optimize the scheduling process time and results. Method : This research was conducted by dividing the scheduling problem into 4 sub – scheduling problems that are sequential, which are the scheduling of the 5 primary courses (lecture, panel discussion, practical sessions, tutorial, and skills laboratory), scheduling topics for each course, student’ group scheduling, and classroom scheduling. The problems are then modeled in the form of integer goal programming. Results: The block system scheduling model in Faculty of Medicine Universitas Gadjah Mada by considering topic and possibility of unavailability room using Sequential Three-Stage Integer Goal Programming has successfully developed and well verified. Conclusion : The model developed in this study is able to produce a schedule that meets all hard constraint in less than 24 hours. The result was more efficient compared to the previous trial-and-error method that consumed 30-45 days.

Background Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the serum and/or liver in HBsAg-negative individuals. OBI is associated with the risk of viral transmission, especially in developing countries, and with progressive liver disease and reactivation in immunosuppressive patients. The objective of this study was to evaluate the relation of OBI to HLA-DP single nucleotide polymorphisms (SNPs) encoding antigen-binding sites for the immune response to HBV infection. As HLA-DP variants affect the mRNA expression of HLA-DPA1 and HLA-DPB1 in the liver, we hypothesised that high levels of HLA-DPA1 and HLA-DPB1 expression favour OBI development. Methods The study enrolled 456 Indonesian healthy blood donors (HBsAg negative). OBI was defined as the presence of HBV-DNA in at least two of four open reading frames (ORFs) of the HBV genome detected by nested PCR. SNPs in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs2281388) were genotyped using real-time Taqman® genotyping assays. Results Of 122 samples positive for anti-HBs and/or anti-HBc, 17 were determined as OBI. The minor allele in rs3077 was significantly correlated with OBI [odds ratio (OR) = 3.87, 95% confidence interval (CI) = 1.58–9.49, p = 0.0015]. The prevalence of the minor allele (T) was significantly higher in subjects with OBI than in those without (59% and 33%, respectively). The combination of haplotype markers (TGA for rs3077–rs3135021–rs9277535) was associated with increased risk of OBI (OR = 4.90, 95%CI = 1.12–21.52 p = 0.038). The prevalence of OBI was highest in the isolated anti-HBc group among the three seropositive categories: anti-HBs

Objective: The long-term administration of a nucleos(t)ide analogue (NA) for the treatment of chronic hepatitis B may encourage the emergence of viral mutations associated with drug resistance. Minor populations of viruses may exist before treatment, but are difficult to detect because of technological limitations. Identifying minor viral quasispecies should be useful in the clinical management of hepatitis B virus (HBV) infection. Methods: Six treatment-naïve Indonesian patients with chronic HBV infection participated in this study. The polymerase region of the HBV genome, including regions with known drug-resistant mutations, was subjected to capillary sequencing and MiSeq sequencing (Illumina). Mutations were analyzed with Genomics Workbench software version 6.0.1 (CLC bio). Results: The mean mapping reads for the six samples was 745,654, and the mean number of amplified fragments ranged from 17,926 to 25,336 DNA reads. Several known drug-resistant mutations in the reverse transcriptase region were identified in all patients, although the frequencies were low (0.12-1.06%). The proportions of the total number of reads containing mutations I169L/M, S202R, M204I/L or N236S were >1.0%. Conclusion: Several known NA-resistant mutations were detected in treatment-naïve patients in Indonesia using deep sequencing. Careful management of such patients is essential to prevent drug-resistant mutations from spreading to other patients.

Background: The traditional learning method applies at Physiology Laboratory of Faculty of Medicine at Universitas Gadjah Mada (UGM) is considered ineffective for the lecturers in managing the students. Moreover, the students perceive that their needs are not adequately accommodated by the lecturers. This downside can be resolved by an alternative learning method which provides conducive, active, creative, effective and enjoyable learning environment called peer assisted learning method. This study is aimed at discovering the students’ perceptions on peer assisted learning method and acquiring the students’ feedback and expectations on the effectiveness of peer-teaching method implementation. Method: The study used cross-sectional design of descriptive research. Results: From the questionnaire analysis with 150 respondents, 90 students of regular program and 60 students of international program, the result according to the frequencies of student perception were: 1) factor 1 were 45.8 % for very high category, 29.8 % for high category, 23.7 % for medium category, 0,8 % for very low category and 0 % for low category; 2) factor 2 were 45 % for high category,41.2 % for medium category,11.5 % for very high category,1.5 % for low category and 0.8 % for very low category; 3) factor 3 were 51.9 % for very high category, 31.3 % for high category,16.0 % for medium category,0.8% for very low category and 0% for low category; 4) factor 4 were 47.3 %for high category, 31.3 % for very high category,19.1 % for medium category,1.5 % for low category and 0.8% for very low category. There was no difference in perception between the students of regular and international program. Responses to open questions and FGD show a variety of students’ feedback and expectation on the peer assisted learning method. Conclusion: The students have shown positive perception on peer assisted learning as a learning method. The peer instructors required in Implementing this model are those students with good communication skill, confirmed academic qualification and capability in managing their fellow students’ learning.