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The seizure incidence in hydrocephalic children has been acknowledged in a lot of studies previously; nonetheless, seizure pathogenesis in these children remains unclear. Its high proportion of hydrocephalic children who underwent shunt surgery suggests that the seizure might be associated with the protocol of shunt placement and/or the shunt existence intracranially; however, this hypothesis could not explain the pre-shunt seizure incidence in hydrocephalic children.This study aims to evaluate the patients' characteristics and CT findings in pre-shunt hydrocephalic children to identify the possible seizure etiology in these patients.Three hundred and thirty-four children with hydrocephalus were included in this study, including 147 hydrocephalic children with the pre-shunt seizure history and 187 hydrocephalic children presented without the pre-shunt seizure history. The following information was retrieved from the patients' medical records: gender, age, pediatric Glasgow Coma Scale (pGCS) upon admission, and hydrocephalus diagnoses. CT findings were re-evaluated to assess the compression association of sulci and gyri, Sylvian fissures, cisterns, FH/ID ratio, Evan's ratio, and periventricular hypodensity with pre-shunt seizure.The results show that the pre-shunt seizure incidence is significantly higher in hydrocephalic children aged 1 to 5 years old (63/113 (55%), p = 0.0001), diagnosed with communicating hydrocephalus (97/163 (59%), p = 0.0001) or infectious hydrocephalus (80/109 (73%), p = 0.0001). The presence of periventricular hypodensity is significantly associated with the pre-shunt seizure incidence (132/205 (64.3%), p = 0.0001). Results from univariate analyses suggest significant association between periventricular hypodensity in every location and pre-shunt seizure (p 0.0001). Multivariate analyses identify that temporal horn in the right lateral ventricle as the location of periventricular hypodensity has the strongest association with the pre-shunt seizure.The presence of periventricular hypodensity in head CT scan is significantly associated with the pre-shunt seizure incidence. Further investigation to confirm this finding and evaluate the possible roles of inflammation in the pre-shunt seizure in hydrocephalic children is important to seek its possible implication on the treatment of pre-shunt seizure in these children.

A number of benign EEG patterns are often misinterpreted as interictal epileptiform discharges (IEDs) because of their epileptiform appearances, one of them is wicket spike. Differentiating wicket spike from IEDs may help in preventing epilepsy misdiagnosis. The temporal location of IEDs and wicket spike were chosen from 143 EEG recordings. Amplitude, duration and angles were measured from the wave triangles and were used as the variables. In this study, linear discriminant analysis is used to create the formula to differentiate wicket spike from IEDs consisting spike and sharp waves. We obtained a formula with excellent accuracy. This study emphasizes the need for objective criteria to distinguish wicket spike from IEDs to avoid misreading of the EEG and misdiagnosis of epilepsy.

Normal weight obesity (NWO) is a new emerging phenotype of obesity, defined as a normal body mass index with a high body fat percentage. While several studies have described the impact of NWO on cardiometabolic risk factors, the association between them remains uncertain. This meta-analysis systematically evaluated cardiometabolic risk factors in adults with NWO compared to adults with normal weight lean (NWL). A systematic literature search was performed from the inception until September 21, 2021 in order to comprehensively search for all observational studies that had three important variables, including adults (age ≥18 years old), NWO and cardiometabolic risk factors including metabolic syndrome, hypertension, diabetes mellitus, dyslipidaemia or all laboratory findings related to cardiometabolic risk factors. Twenty-four cross-sectional studies with a total of 75 201 subjects are included in the qualitative and quantitative analysis. Overall, older age and female sex are more likely in NWO population. Compared to NWL, NWO is significantly associated with cardiometabolic risk factors, including metabolic syndrome (OR = 2.24 [1.74, 2.89]; p .001; I

Background Neonatal jaundice is a common finding in newborns in Asia, including Indonesia. In some cases, the serum total bilirubin levels exceeds the 95th percentile for hours of life (neonatal hyperbilirubinemia). Severe neonatal hyperbilirubinemia (NH) could lead to kernicterus and neonatal death. Glucose-6-Phosphage Dehydrogenase (G6PD) genetic variations and deficiency have been reported in several studies to be associated with NH. This study aimed to analyze the G6PD genetic variations and its activity in neonates with and without hyperbilirubinemia in the Deutromalay Indonesian population. Methods Deoxyribose Nucleic Acid (DNA) was isolated from peripheral blood of 116 and 115 healthy term neonates with and without hyperbilirubinemia. All infants underwent the following laboratory examinations: routine hematologic evaluation, Coombs test, G6PD activity measurement using the Randox kit method, and serum total bilirubin level. All exons of the G6PD gene were targeted for deep sequencing using MiSeq (Illumina). An association study of G6PD polymorphisms with NH was performed using PLINK. Results The prevalence of G6PD deficiency in neonates with and without hyperbilirubinemia in Indonesian Deutromalay population were 1.72% (95% Confidence Interval (CI): 0.6–4.1%) and 1.74% (95% CI: 0.7–4.1%), respectively. The most common G6PD polymorphisms, i.e. rs1050757/c.* + 357A > G, rs2230037/c.1311C > T, and rs2071429/c.1365-13 T/IVS11, were identified. However, none of those polymorphisms and their haplotype were associated with NH (p > 0.05, Odds Ratio (OR) ~1.00). The prevalence of G6PD mutations in neonates with and without hyperbilirubinemia were 6.8% (95% CI: 2.3–11.5%) and 6.9% (95% CI: 2.3–11.6%), respectively. The most frequently identified G6PD mutation was the Viangchan variant (p.V291 M), which was followed by the Canton (p.R459L) and Vanua Lava (p.L128P) variants. Two novel mutations were identified both in case (p.V369A, p.I167F) and control (p.L474=, p.I36T) groups. Conclusion The prevalence of G6PD deficiency is low in neonates with or without hyperbilirubinemia in Deutromalay Indonesian population. The majority of G6PD mutations identified among Indonesian Deutromalay population in this study are Viangchan, Canton and Vanua Lava variants.

Estradiol is a steroid hormone that works as an agonist estrogen receptor (ER). This compound is widely used as a ligand and bind specifically to the ERα. Radioligand binding assay is an in vitro method for drug development from natural products by synthesizing estradiol through radiolabeling using the radioiodination method. Synthesis of 131I-estradiol was perfomed by direct method using chloramine T as an oxidizer and by indirect labeling using 131I-histamine. The purity of chemical was determined by thin-layer chromatography and paper electrophoresis, as well as its stability for 30 days of storage in refrigerator, freezer and room temperature. The cellular uptake test of the radioligands from both methods was carried out with MCF7 and T-47D cell lines at 60 min. The results exhibited that 131I-estradiol was succesfully obtained with radiochemical purity greater than 95% and more stable in the refrigerator until 21 days than freezer and room temperature. 131I-estradiol and 131I-his-estradiol were internalized higher in T-47D cells than MCF7 cells (44.34 ± 5.93% vs. 17.27 ± 1.71% and 45.34 ± 6.42% vs. 4.92 ± 1.59%, respectively). Furthermore, the radioligands can be used to binding assay in determining the agonist or antagonist to ER of new drugs development.

Spinocerebellar ataxia (SCA) is an autosomal dominant hereditary disease with progressive course, and no causal therapy. Diagnostics are still challenging, due to facility and protocols, and so as in Indonesia. As a national referral center, Dr. Hasan Sadikin Central General Hospital has received a lot of patients from all over Indonesia, particularly from Western Java. Study related to SCA (including clinical and genetic profile) is still limited in Indonesia. We identified index patients from three families with ataxia, hence intend to determine their clinical and genetic pattern. The hereditary pattern is autosomal dominant. Scale for the assessment and rating of ataxia (SARA) shows mild and moderate ataxia. Inventory of non-ataxia signs (INAS) scores of the patients were 3, 5 and 6. Montreal cognitive assessment-Indonesian version (MOCA-INA) shows only one patient has mild cognitive impairment, despite young age. Barthel index shows 1 subject has moderate dependency. Mutation in Ataxin3 polyQ repeats shows pathologically long CAG repeats, 72,10; 72,10; and 72,23 respectively in mutant and wild type allele. We diagnosed the index patients with spinocerebellar ataxia type 3. This study is the first case series study in Indonesia. The hereditary pattern is clearly shown as an autosomal dominant ataxia. The clinical and genetic profile was varied, and the symptom is progressive and deteriorates overtime, including wide based gait, speech problem, motor and sensor complaint, and cognitive decline complaint. Despite the same polyQ stretch length, the onset and clinical characteristics of patients are diverse., Autosomal dominant, Familial ataxia, Indonesia, Polyglutamine, Spinocerebellar ataxia.

AIM: This study aims to investigate the effect of ATP, EGF and combination of those two to the Natrium Iodide Symporter (NIS) expression in MCF7, SKBR3 and HaCaT cell lines. METHODS: MCF7, SKBR3 and HaCaT cell lines were treated with ATP, EGF and combination of those two for 6, 12 and 24 hours. The expression of NIS mRNA was measured through quantitative-reverse transcription-polymerase chain reaction (qRT-PCR). The NIS protein expression was confirmed by immunocytofluorescence. RESULTS: NIS mRNA was expressed in SKBR3 and HaCaT cell lines but not in MCF7. The levels of NIS mRNA expression, after treatment by epidermal growth factor (EGF), adenosine Tri-Phosphate (ATP) or the combination of both for 6 and 12 hours were not significantly different from those of untreated cells. However, the treatment by a combination of ATP and EGF for 24 hours increases the level of NIS mRNA expression by 1.6 fold higher than that of the untreated cells (1.6241 ± 0.3, p < 0.05) and protein NIS expression increase significantly by the treatment than untreated cells (P < 0.05). CONCLUSION: The level of NIS expression varies among the different subtypes of breast cancer cell lines. MCF7 cell line is representing the luminal A subtype of breast cancer does not express NIS. Only SKBR3 cell line express NIS and this subtype might be suitable to receive radioiodine therapy as those cells expressing NIS. A combination treatment of EGF and ATP increases the expression of NIS mRNA and protein at the membrane in SKBR3 cells.

Background: Nutmeg (Myristica fragrans Houtt) has the potential to control blood glucose and lipid levels. However, it contains safrole compounds, which are dangerous when humans consume them. Objective: In this study, we eliminated safrole from nutmeg and investigated its antidiabetic and antidyslipidemic properties. Methods: Nutmeg seeds were powdered, extracted with 90% ethanol, and chromatographed to remove the safrole. Safrole-free nutmeg extract was concentrated, and its antidiabetic and antidyslipidemic agents were tested in a type 2 diabetes mellitus rat model. Results: The results showed that the blood glucose level decreased by 20% after 2 days of treatment, 30% after 4 days of treatment and 40% after 6 days of treatment with nutmeg extracts. The blood triglyceride level did not change in the first 2 days of treatment, and it decreased by 25% after 4 days of treatment and by another 25% after 6 days of treatment. Luciferase assay showed that safrole- free nutmeg increased the activities of PPAR α and γ in a dose-dependent manner, which marked the potential mechanism of lowering the triglyceride and glucose levels. Conclusion: Results thus obtained are suggestive of the potential dual effect of safrole-free nutmeg extract on antidiabetic and antidyslipidemic management.

Summary Convalescent plasma therapy (CPT) has been investigated as a treatment for COVID‐19. This review evaluates CPT in COVID‐19 and other viral respiratory diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. PubMed and Google scholar databases were used to collect eligible publications until 8 December 2020. Meta‐analysis used Mantel–Haenszel risk ratio (RR) with 95% confidence interval (CI) and pooled analysis for individual patient data with inverse variance weighted average. The study is registered at PROSPERO with the number of CRD4200270579. Forty‐four studies with 36,716 participants were included in the pooled analysis and 20 studies in the meta‐analysis. Meta‐analysis showed reduction of mortality (RR 0.57, 95% CI [0.43, 0.76], z = 3.86 [p

Background Various techniques in assisted reproductive technology (ART) have been developed as solutions for specific infertility problems. It is important to gain consensual conclusions on the actual risks of neurodevelopmental disorders among children who are born from ART. This study aimed to quantify the relative risks of cerebral palsy, intellectual disability, autism spectrum disorder (ASD), and behavioral problems in children from different ART methods by using systematic review and meta-analysis. Healthcare providers could use the results of this study to suggest the suitable ART technique and plan optimum postnatal care. Methods Pubmed, Google Scholar, and Scopus databases were used to search for studies up to January 2020. Of the 181 screened full manuscripts, 17 studies (9.39%) fulfilled the selection criteria. Based on the Newcastle-Ottawa scale ratings, 7 studies were excluded, resulting in 10 studies that were eventually included in the meta-analyses. Mantel-Haenszel risk ratio model was used in the meta-analysis, and the results are described using forest plot with 95% confidence interval. Heterogeneity was assessed using the I2 value. Results Pooled evaluation of 10 studies showed that the risk of cerebral palsy in children from assisted reproductive technology (ART) is higher than children from natural conceptions (risk ratio [RR] 1.82, [1.41, 2.34]; P = 0.00001). Risk of intellectual disability (RR 1.46, [1.03, 2.08]; P = 0.03) and ASD (RR 1.49 [1.05, 2.11]; P = 0.03) are higher in intracytoplasmic sperm injection (ICSI) children compared to conventional in vitro fertilization (IVF) children. The differences in the risk of neurodevelopmental disorders in children born after frozen and fresh embryo transfers are not significant. Analysis on potential cofounder effects, including multiple birth, preterm birth, and low birth body weight highlight possibilities of significant correlation to the risks of neurodevelopmental disorders. Conclusions Pooled estimates suggest that children born after ART are at higher risk of acquiring cerebral palsy. ICSI treatment causes higher risk of intellectual disability and ASD. These findings suggest the importance of the availability of intensive care unit at the time of delivery and long-term developmental evaluation particularly in children from ICSI.

Hydrocephalus is diagnosed when an accumulating amount of cerebrospinal fluid (CSF) fails to circulate and/or absorbed in the ventricular system. Based on its etiology, hydrocephalus can be classified into infectious and non-infectious hydrocephalus. In children, non-infectious hydrocephalus includes congenital hydrocephalus, posthemorrhagic hydrocephalus, neural tube defect–related hydrocephalus, and tumor-related hydrocephalus. Regardless of the cause, a CSF diversion device is placed to divert the excess fluid from the ventricles into peritoneal cavity. Among all, ventriculoperitoneal (VP) shunt is arguably the most commonly used CSF diversion device to date. Until now, the long-term neurodevelopmental impact of VP shunt placement in non-infectious hydrocephalus patients remained unclear. This study aims to evaluate the neurodevelopmental outcomes in children with non-infectious hydrocephalus who had VP shunt placement. Systematic searches were performed using PubMed, Google Scholar, Scopus databases, and reference lists. Publications that fulfilled the inclusion criteria were included in the meta-analysis. Calculation of Mantel-Haezel risk ratio (RR) was applied, and heterogeneity index (I2) test was used to evaluate the existence of heterogeneity in all studies. Risk of bias was assessed based on the criteria from the Newcastle-Ottawa Scale (NOS). Of the 1929 studies identified, 12 publications were concluded to have fulfilled the inclusion criteria. Results from the meta-analysis showed that the risks of cerebral palsy, visual and hearing impairment, epilepsy, or seizures are significantly higher in children with non-infectious hydrocephalus who already had VP shunt placement (shunted non-infectious hydrocephalus, S-NIH) compared to that of the healthy control. The meta-analysis on intelligent quotient (IQ) and mental development index (MDI) showed that S-NIH children tend to score lower IQ and acquire risk of having mental development delay. On motoric development, S-NIH children scored lower motoric score and have significantly higher risk of motor development delay compared to control. Although normal children tend to have more internalizing behavior compared to S-NIH children, overall assessment on the risk of behavioral abnormalities showed that the differences between these two groups are insignificant. S-NIH children have significantly higher risks of disabilities and mental and motoric development delays; thus, planning on continuous rehabilitation for children with non-infectious hydrocephalus who already had placement of VP shunt is important to acquire their optimum potentials and quality of life.

Introduction: In addition to antiviral medication, Convalescent plasma therapy (CPT) has also been investigated for COVID-19 treatment. This study aimed to evaluate CPT potentials in COVID-19 treatment, by performing systematic review and meta-analysis of studies in COVID-19 and other similar viral respiratory diseases, including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and Influenza. Method: PubMed and Google scholars database were used to collect publications up to June 6, 2020. We included all studies reported clinical outcomes of severe to critically ill viral respiratory diseases patients. Review/systematic review/meta-analysis and articles not written in English, ineligible for full-access were excluded. Meta-analysis used Mantel-Haezel Risk Ratio (RR) with 95% confidence interval for dichotomous data, while mean difference was calculated for continuous data with random effect model. Pooled analysis for individual patients data were performed with Inverse Variance Weighted Average using random effect model. The study is registered with PROSPERO, number CRD42020190579. Result: Our search identified 3,786 studies. Nineteen studies with 436 participants were included in the meta-analysis. Pooled analysis showed reduction of mortality [RR 0.46 (0.24, 0.86), z=2.41(p=0.02), I 2 =68% (p=0.003)] and higher number of discharged patients [RR 1.28 (1.12, 1.46), z=3.61 (p=0.0003), I 2 =73% (p=0.002)] in CPT groups. The mean time to discharge in COVID-19 patients after receiving CPT is 18.35 days. Possible CPT mechanism of action is due to its ability to immediately reduce viral titer [Mean diff -0.68(-0.94, -0.41), z=5.03 (p

Gastric cancer is the second leading cause of cancer-related mortality and the fourth most common cancer globally. Gastric premalignant lesions are well known risk factors for the development of gastric cancer. The purpose of this study was to investigate the risk factors of gastric premalignant lesion. This cross-sectional study observed gastritis patients at Adam Malik General Hospital, Permata Bunda General Hospital, Universitas Sumatera Utara Hospital, all located in Medan, Indonesia. A total of 120 gastritis patients were included in this study. Patients were interviewed with a questionnaire to obtain demographic data, alcohol intake, smoking status, high salt diet and NSAID use. Diagnosis of Helicobacter pylori infection was made using positive results of the carbon-14 urea breath test (14C-UBT), rapid urease test, and/or immunohistochemistry. Endoscopy and biopsy were conducted to diagnose gastric premalignant lesion. Gastric premalignant lesion diagnosis was made when one or more of the following were present: Chronic atrophic gastritis, intestinal metaplasia, or dysplasia. Data were analysed using SPSS version 22. There were 35/120 (29.2%) of gastritis patients having gastric premalignant lesion. Multivariate analysis has shown that H. pylori infection, patients with family history of gastric cancer, alcohol consumption and Batak ethnic have increased risk to develop gastric premalignant lesion (p

AIM: To evaluate the association between VEGF-634G>C gene polymorphism with premalignant gastric lesions as well as the level of VEGF.METHODS: This cross-sectional study included patients with H. pylori gastritis at Haji Adam Malik General Hospital, Permata Bunda General Hospital, and Universitas Sumatera Utara Hospital, Medan, Indonesia. Detection of H. pylori infection was made using positive results of 14C-UBT, rapid urease test, and/or immunohistochemistry. Gastric premalignant lesion diagnosis was made when one or more of the following were present: chronic atrophic gastritis, intestinal metaplasia, or dysplasia. Real-time polymerase chain reaction (RT-PCR) was used to examine VEGF-634G>C gene polymorphism. Additionally, serum samples of patients with H. pylori gastritis were obtained to determine the level of circulating VEGF. Data were analysed using SPSS version 22.RESULTS: A total number of 87 patients with H. pylori gastritis were included in this study. Of all participants, 26 patients (29.9%) showed gastric premalignancy. There was a significant association between GG+GC genotype of VEGF-634G>C and gastric premalignant lesions (P = 0.003; OR (CI 95%) = 6.07 (1.88-41.71)). VEGF-634 G>C polymorphism also showed an association with VEGF serum levels (P = 0.005). Patients with the GG+GC genotype would be at risk of 3.16 times to have high VEGF levels compared to CC genotypes.CONCLUSION: VEGF-634G>C polymorphism, in particular, GG+GC genotype was associated with an increased risk of gastric premalignant transformation as well as having high VEGF levels in patients with H.pylori gastritis.

Indonesia adalah negara dengan jumlah penderita tuberkulosis (TB) terbanyak kedua di dunia. Diabetes melitus (DM) merupakan salah satu komorbid TB. Arylamine N-acetyltransferase 2 (NAT2) adalah enzim yang berfungsi memetabolisir isoniazid (INH) yang disandi oleh gen NAT2 . Gen NAT2 memiliki sejumlah polimorfisme dan dapat menentukan kemampuan seseorang untuk memetabolisir obat yang disebut status asetilator. Pada individu dengan status asetilator lambat, INH dimetabolisir dengan lambat sehingga memungkinkan terjadi intoksikasi hati. Pada TB dengan DM (TBDM) status asetilator lambat dapat membuat pengobatan TB maupun DM menjadi kurang optimal. Penelitian ini bertujuan mengeksplorasi status asetilator pasien TBDM di RSUD Prof. WZ Johannes Kupang periode Juni–November 2011. Pada penelitian potong lintang ini DNA dari darah 122 pasien TB diisolasi dan gen NAT2 kemudian diamplifikasi dan disekuensing untuk diketahui status asetilatornya. Hasil penelitian menunjukkan terdapat 5 pasien yang memiliki glukosa serum >200 mg/dL yang dikategorikan sebagai pasien TBDM. Pada pasien TBDM didapatkan seorang dengan status asetilator cepat (NAT2*4/NAT2*4), 2 orang dengan status asetilator sedang (NAT2*13A/NAT2*6J), dan 2 orang dengan status asetilator lambat (NAT2*5/NAT2*5G, NAT2*6A/ NAT2*6A, NAT2*7B/ NAT2*7B). Pada pasien TB yang dipilih secara random berdasar usia dan jenis kelamin serupa dengan TBDM didapatkan 2 orang dengan status asetilator cepat (NAT2*4/NAT2*4) dan 3 orang dengan asetilator sedang (NAT2*4/NAT2*6A, NAT2*13A/NAT2*6J). TBDM yang memiliki status asetilator lambat berpotensi memiliki masalah ganda dalam terapi, selain dapat terjadi toksisitas hati akibat terapi dengan INH, juga dapat mengakibatkan pengobatan DM menjadi tidak optimal. Perlu dilakukan peneltian lebih lanjut terkait farmakogenetik pada TBDM. [ MKB. 2016;49(1):61–6] Kata kunci : Asetilator, isoniazid, NAT2 , farmakogenetik, tuberkulosis NAT2 Gene Acetylator Status of Tuberculosis and Tuberculosis with Diabetes Mellitus Patients in Kupang, Nusa Tenggara Timur Indonesia is the second highest country with TB patients in the world. Diabetes mellitus (DM) is a comorbid of TB. Arylamine N-acetyltransferase 2 (NAT2), encoded by the NAT2 gene, is an enzyme that metabolizes isoniazid (INH). NAT2 gene has some polimorphysims that may play a role in INH acetylating process. Those who are slow acetylators may develop liver intoxication as a consequence of slow INH metabolism process. Slow acetylator TBDM patients may complicate both TB and DM treatment, causing them to be less optimal. The aim of this study was to explore the acetylator status of TBDM patients in Kupang, Indonesia. A cross-sectional study was conducted by obtaining DNA of 122 TB patients in Kupang in June–November 2011. NAT2 gene was amplified and sequenced to determine the acetylator status. There were 5 TB patients who had a glucose serum level of >200mg/dL and was catagorized as TBDM. Result showed that there was 1 TBDM patient who was a rapid acetylator (NAT2*4/NAT2*4), 2 patients as intermediate acetylators (NAT2*13A/NAT2*6J), and 2 patients as slow acetylators (NAT2*5/NAT2*5G, NAT2*6A/ NAT2*6A, NAT2*7B/ NAT2*7B). Meanwhile, there were 2 TB patients who was rapid acetylators (NAT2*4/NAT2*4) and 3 patients as intermediate acetylators (NAT2*4/NAT2*6A, NAT2*13A/NAT2*6J). Slow NAT2 acetylator TBDM patients potentially face more problems during therapy. As INH may cause liver intoxication, these patients may also experience unoptimum DM treatment. Therefore, it is strongly recommended to do a study on the role of pharmacogenomics in TBDM. [ MKB. 2016;49(1):61–6] Key words: Acetylator, isoniazid, NAT2 , pharmacogenetics, tuberculosis

Immunopathology contributes to high mortality in tuberculous meningitis (TBM) but little is known about the blood and cerebrospinal fluid (CSF) immune response. We prospectively characterised the immune response of 160 TBM suspects in an Indonesian cohort, including 67 HIV-negative probable or definite TBM cases. TBM patients presented with severe disease and 38% died in 6 months. Blood from TBM patients analysed by flow cytometry showed lower αβT and γδT cells, NK cells and MAIT cells compared to 26 pulmonary tuberculosis patients (2.4-4-fold, all p ex-vivo stimulation of whole blood showed a much broader range in TBM compared to both control groups (p ex-vivo production of TNF-α, IL-6 and IL-10 correlated with fever, lymphocyte count and monocyte HLA-DR expression (all p

Indonesia has been practicing both symmetric and asymmetric decentralization for decades. This study believes that asymmetric decentralization should not only for those five provinces (Jakarta, Yogyakarta, Aceh, Papua and West Papua). If political considerations and the effectiveness and efficiency of government, asymmetric decentralization becomes a necessary choice for many other regions in Indonesia. This includes autonomous regions characterized by islands (archipelagic regions). Hence, this paper will discuss a number of reasons why archipelagic regions also need asymmetrical arrangements. How to make such arrangements functional? What potential challenges might be encountered? This study employs qualitative approach with theory-driven type. Operationally, this study is sustained by a series of Focus Group Discussion (FGD) and documentary method. Aiming at strengthening the capacity of the government for more effective governance and development process, the uniqueness and various specific problems faced by archipelagic regions become the main reasons for applying asymmetric decentralization. Proposing a separate policy provides an effective strategy for certainty and functional de jure and de facto asymmetry arrangements. Handling various existing problems which could weaken the capacity to carry out asymmetric decentralization policy would be the most appropriate strategy to make the policy facilitates its potential benefits.

Objective: To observe the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and homocysteine levels in cerebral palsy (CP) children. Methods: This cross-sectional study was conducted in several hospitals, school for children with special needs, and rehabilitation centers in Bandung from March to November 2014, on children with CP aged 4–14 years who met the inclusion criteria. Genotyping was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and direct sequencing. Homocysteine serum level was measured using chemiluminescent microparticle immunoassay (CMIA) method. Statistical analysis was conducted using t test. Results: In this study, 150 CP children had MTHFR C677T gene polymorphism with a frequency of 18%, consisting of TT homozygotes (4%), CT heterozygotes (14%), and T allele (11%. The mean serum level of homocysteine in CP with C677T MTHFR gene polymorphism was 8.22 (±1.89) µmol/L, higher than those without polymorphism (p=0.046). Conclusions: A relationship between MTHFR C677T gene polymorphism and homocysteine level in children with cerebral palsy is found in this study. Keywords: Cerebral palsy, homocysteine, methylenetetrahydrofolate reductase polymorphism DOI: 10.15850/ijihs.v4n1.682

Galur se l SKBR3 adalah model kanker payudara positif human epidermal growth factor receptor2 (HER2). Pemberian kemoterapi memperlihatkan respons lengkap hanya pada 50% pasien kanker payudara dengan tipe positif HER2. Kemampuan jaringan tumor menangkap dan mengakumulasi iodium radioaktif dihubungkan dengan ekspresi natrium/iodide symporter (NIS). Tujuan penelitian ini adalah menilai ekspresi dan distribusi NIS pada galur sel SKBR3 serta menilai efek induksi epidermal growth factor (EGF) pada ekspresi NIS menggunakan imunositofluoresens-ISF . Penelitian ini dilakukan di Laboratorium Kultur Sel, Fakultas Kedokteran Universitas Padjadjaran (FKUP) mulai bulan September 2013 sampai dengan April 2014. Sel SKBR3 ditumbuhkan pada plat kultur dan ditunggu hingga konfluen 70%. Sel dibagi atas dua kelompok, yaitu kelompok yang diberi induksi dan kontrol. Induksi EGF diberikan dengan dosis 50 ng/mL. Pemeriksaan ISF menggunakan antibodi primer rabbit polyclonal antibody anti NIS dan antibodi sekunder goat anti rabbit IgG polyclonal antibody . Data hasil pengamatan dinilai secara semikuantitatif. Natrium/iodide symporter tampak terekspresi dan terdistribusi di sitoplasma. Sel yang diinduksi dengan EGF memperlihatkan peningkatan ekspresi NIS di sitoplasma dan distribusinya di membran sel secara bermakna. Sel SKBR3 mengekspresikan NIS yang terdapat di sitoplasma. Induksi EGF meningkatkan ekspresi NIS dan distribusinya di membran sel. Temuan ini dapat mengarah potensi kemampuan sel kanker payudara menangkap dan mengakumulasikan iodium radioaktif. [ MKB . 2016;48(1):15–8] Kata kunci: Ekspresi NIS , galur sel SKBR3, kanker payudara, imunositofluoresens Detection of Natrium/Iodide Symporter (NIS) in SKBR-3 Breast Cancer Cell Line Using Immunocytofluoresence Abstract SKBR-3 cell line is a breast cancer model for human epidermal growth factor receptor2 (HER2) positive. Only 50% of patients of this type have fully responded to chemotherapy. Natrium iodide symporter expression correlates with the uptake and ability of cells to accumulate radioiodine. The aim of this study was to examine natrium/iodide symporter (NIS) expression and its distribution with and without epidermal growth factor (EGF) treatment using immunocytofluoresence (ICF). This study was conducted at the Cell Culture Laboratory, Faculty of Medicine, Universitas Padjadjaran from September 2013 to April 2014. SKBR3 cells were cultured until 70% confluent. Cells were then divided into two groups: treatment group and control group. The treatment group was treated with EGF 50 ng/mL. Cells were incubated with primary antibody rabbit polyclonal antibody anti-NIS, and then were followed with secondary-antibody goat polyclonal antibody to rabbit. Data from the observation were then assessed semi-quantitatively. Natrium/iodide symporter was seen to be expressed and distributed in the cytoplasm. Cells induced by EGF showed significant increase in NIS expression in cytoplasm and its distribution in cell membrane. It is concluded that the SKBR3 cells express NIS in cytoplasm and that EGF induction increases NIS expression and distribution in cell membrane. This finding leads to a potential ability of breast cancer cells to uptake and accumulate radioiodine. [ MKB . 2016;48(1):15–8] Key words: Breast cancer, cell line SKBR-3, immunocytofluoresence, NIS expression

BackgroundHigh doses of rifampicin may help tuberculous meningitis (TBM) patients to survive. Pharmacokinetic-pharmacodynamic evaluations suggested that rifampicin doses higher than 13 mg/kg intravenously or 20 mg/kg orally (as previously studied) are warranted to maximize treatment response.MethodsIn a double-blinded, randomised, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg or 1350 mg (10, 20 and 30 mg/kg) oral rifampicin combined with other TB drugs for 30 days. Endpoints included pharmacokinetic measures, adverse events and survival.ResultsA double and triple dose of oral rifampicin led to three and five-fold higher geometric mean total exposures in plasma in the critical early days (2±1) of treatment (AUC0-24h: 53·5 mg.h/L vs 170·6 mg.h/L vs. 293·5 mg.h/L, pConclusionsTripling the standard dose caused a large increase in rifampicin exposure in plasma and CSF and was safe. Survival benefit with this dose should now be evaluated in a larger phase III clinical trial.

BACKGROUND: Immunopathology contributes to the high mortality of tuberculous meningitis, but the biological pathways involved are mostly unknown. We aimed to compare cerebrospinal fluid (CSF) and serum metabolomes of patients with tuberculous meningitis with that of controls without tuberculous meningitis, and assess the link between metabolite concentrations and mortality.METHODS: In this observational cohort study at the Hasan Sadikin Hospital (Bandung, Indonesia) we measured 425 metabolites using liquid chromatography-mass spectrometry in CSF and serum from 33 HIV-negative Indonesian patients with confirmed or probable tuberculous meningitis and 22 control participants with complete clinical data between March 12, 2009, and Oct 27, 2013. Associations of metabolite concentrations with survival were validated in a second cohort of 101 patients from the same centre. Genome-wide single nucleotide polymorphism typing was used to identify tryptophan quantitative trait loci, which were used for survival analysis in a third cohort of 285 patients.FINDINGS: Concentrations of 250 (70%) of 351 metabolites detected in CSF were higher in patients with tuberculous meningitis than in controls, especially in those who died during follow-up. Only five (1%) of the 390 metobolites detected in serum differed between patients with tuberculous meningitis and controls. CSF tryptophan concentrations showed a pattern different from most other CSF metabolites; concentrations were lower in patients who survived compared with patients who died (9-times) and to controls (31-times). The association of low CSF tryptophan with patient survival was confirmed in the validation cohort (hazard ratio 0·73; 95% CI 0·64-0·83; pINTERPRETATION: Cerebral tryptophan metabolism, which is known to affect Mycobacterium tuberculosis growth and CNS inflammation, is important for the outcome of tuberculous meningitis. CSF tryptophan concentrations in tuberculous meningitis are under strong genetic influence, probably contributing to the variable outcomes of tuberculous meningitis. Interventions targeting tryptophan metabolism could improve outcomes of tuberculous meningitis.FUNDING: Royal Dutch Academy of Arts and Sciences; Netherlands Foundation for Scientific Research; Radboud University; National Academy of Sciences; Ministry of Research, Technology, and Higher Education, Indonesia; European Research Council; and PEER-Health.

High doses of rifampin may help patients with tuberculous meningitis (TBM) to survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin doses higher than 13 mg/kg given intravenously or 20 mg/kg given orally (as previously studied) are warranted to maximize treatment response. In a double-blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg, or 1,350 mg (10, 20, and 30 mg/kg) oral rifampin combined with other TB drugs for 30 days. The endpoints included pharmacokinetic measures, adverse events, and survival. A double and triple dose of oral rifampin led to 3- and 5-fold higher geometric mean total exposures in plasma in the critical early days (2 ± 1) of treatment (area under the concentration-time curve from 0 to 24 h [AUC(0–24)], 53.5 mg · h/liter versus 170.6 mg · h/liter and 293.5 mg · h/liter, respectively; P

Neonatal hyperbilirubinemia (NH) is a common finding in newborn babies in Indonesia. Common and rare variants of UGT1A1 have been known to contribute to NH etiology. This study aims to identify UGT1A1 genetic variation and haplotype associated with NH in Indonesian population. DNA was isolated from 116 cases and 115 controls and a targeted-deep sequencing approach was performed on the promoter, UTRs, and exonic regions of UGT1A1. Determining association of common variants and haplotype analysis were performed using PLINK and Haploview. Ten and 4 rare variants were identified in cases and controls, respectively. The UGT1A1 rare variants frequency in cases (5.17%) was higher than that in controls (1.7%). Four of those rare variants in cases (p.Ala61Thr, p.His300Arg, p.Lys407Asn, and p.Tyr514Asn) and three in controls (p.Tyr79X, p.Ala346Val, and p.Thr412Ser) are novel variants. The frequencies of p.Gly71Arg, p.Pro229Gln, and TA7 common variants were not significantly different between cases and controls. A haplotype, consisting of 3 major alleles of 3′ UTRs common variants (rs8330C>G, rs10929303C>T, and rs1042640C>G), was associated with NH incidence (p=0.025) in this population. Using targeted-deep sequencing and haplotype analysis, we identified novel UGT1A1 rare variants and disease-associated haplotype in NH in Indonesian population.

Imminent abortion needs more serious attention since it remains a big problem in Indonesia considering its epidemiology, morbidity, mortality, and prognosis. In fact, some cases can still be prevented. The objective of this study was to determine pathogenesis, diagnosis, and prognosis of imminent abortion through the role of antioxidant vitamin C in the interaction of superoxide dismutase (SOD), interferon-γ (IFN-γ), interleukin-4 (IL-4), vascular cells adhesion molecule-1 (VCAM-1), and decidual spiral artery resistance index (DSA RI). This study took 10 months from March to December 2007 at Obstetrics and Gynecology Department of Medical Faculty of Padjadjaran University/Hasan Sadikin Hospital, Bandung. Sixty pregnant women who met the inclusion and exclusion criteria were divided into two groups with the random clinical trial method, double-blind with repeated measurements. Data were analyzed statistically using t test, Mann-Whitney, Rank Spearman, Wilcoxon, t paired, and diagnostic test. The results of this study showed that the incidence of abortion in vitamin C group was 9 cases (30%) and placebo group was 13 cases (43.3%). There was a significant difference in SOD, IFN-γ, IL-4 and VCAM-1 level between groups of women with and without abortion (p ￡992 U/gHbwhich showed quite high sensitivity, specificity, accuracy, and significant difference (p γ, VCAM-1 and DSA RI (p γ level and the increase of IL-4 level in imminent abortion after vitamin C administration. There was a correlation between the increase of SOD level with the decrease of DSA RI and the decrease of VCAM-1 level in imminent abortion after vitamin C administration. In abortion, there was a decrease of SOD and IL-4 level, as well as an increase of IFN-γ, VCAM-1, and DSA RI level.