Alteration in 11 Beta-Hydroxysteroid Dehydrogenase Type-2 (HSD11B2) Gene as A Potential Candidate Parameter for Early Detection of Intrauterine Growth Restriction (IUGR) Events

Intrauterine Growth Restriction (IUGR) incidence in Indonesia ranks in the top 10 of the highest in Asia. It is the main perinatal death cause. IUGR also impairs fetal neurodevelopment, which can affect the development of children until later ages. Lack of 11β-hydroxysteroid dehydrogenase type-2 (11β-HSD2) enzyme is influenced by changes in the coding gene, HSD11B2, one of IUGR's causes. The main diagnostic method of IUGR at this time is by using Doppler ultrasound. However, Doppler ultrasound has several limitations as many cases are not detected. Its clinical predictive value in various women is poor, as Doppler ultrasound is not recommended for use in the first trimester, detection of abnormalities in the second trimester seems to be too late for helpful interventions. The study aim is to present an overview concerning HSD11B2 gene alteration in an non-invasive prenatal testing (NIPT) as a possible diagnostic parameter for early detection in IUGR infants. This literature review is based on selected articles and studies taken from the Pubmed, Proquest, and EBSCO databases. A total of 4 studies reported the tendency for DNA methylation and decreased expression of the HSD11B2 gene in IUGR cases. Changes in the HSD11B2 gene have the potential to become a diagnostic parameter in the early detection of infants with IUGR. Further study and investigation of this possibility are needed.Keywords: intrauterine growth restriction, HSD11B2, early detection, diagnostic, non-invasive prenatal testing

Association of Hypertension and Chronic Kidney Disease in Population Aged ≥18 Years Old

Background: Chronic kidney disease (CKD) is a global public health problem, due to the increasing prevalence and incidence of kidney failure, poor prognosis, and required high costs for its treatment. Hypertension as the dominant risk factor for CKD also has a high prevalence which keep increasing in DKI Jakarta. This study aimed to determine the association between hypertension and the incidence of CKD in people aged ≥18 years old in DKI Jakarta Province.Materials and method: This was a quantitative research with an analytic cross-sectional study design. The data source used was secondary data obtained from Basic Health Research (Riset Kesehatan Dasar/Riskesdas) 2018. There were 7,141 samples that matched the inclusion and exclusion criteria.Results: The proportion of CKD and hypertension in people aged ≥18 years old in DKI Jakarta Province were 0.5% and 16.6%, respectively. There was a significant association between hypertension and CKD with a prevalence odds ratio (POR) of 3.140 (95% CI: 1.527-6.453) after being adjusted by the age variable. Several other characteristics such as age (POR = 3.912; 95% CI: 1.932-7.918), diabetes mellitus (POR = 3.412; 95% CI: 1.405-8.285), heart disease (POR = 7.323; 95% CI: 3.158- 16.982), and physical activity (POR = 2.324; 95% CI: 1.148-4.703) were also significantly associated with the incidence of CKD.Conclusion: Someone who has hypertension has 3.14 times (95% CI: 1.527-6.453; p-value = 0.002) chance of suffering from CKD compared to someone who does not have hypertension after being controlled by the confounding variable, age.Keywords: chronic kidney disease, hypertension, DKI Jakarta, Basic Health Research 2018

Validation of a Liquid Chromatography/Tandem Mass Spectrometry Assay for the Quantification of Plasma Dihydroartemisinin

Background: Insufficient plasma level of dihydroartemisinin (DHA) can select resistance and will further hinder malaria elimination program. We investigated clinical applicability of a validated liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay to quantify plasma concentration of DHA in healthy subjects from a single oral administration of fixed dose combination of Dihydroartemisinin-Piperaquine.Materials and Methods: Micro-elution solid-phase extraction in a 96-well plate format was used to prepare the samples. DHA separation happened in Acquity UPLCTM BEH C18 column (50 × 2.1 mm, 1.7 µm). Mobile phase was a mixture of acetonitrile-ammonium acetate 10 mM pH 3.5 (50:50, v/v) at 0.3 mL/minute flow rate. Waters Acquity UPLC™ H-Class system coupled with triple quadruple mass spectrometry in positive electrospray ionization mode was used for detection. The internal standard was a stable isotope labelled DHA.Results: Calibration curve was linear with a correlation coefficient >0.995 over a concentration range of 1–1,000 ng/mL. Bias and variation for accuracy and precision were in the range of 15% (20% at the lower limit of quantification). Using 5 µL sample, lower limit of quantification was 1 ng. Matrix effect was less than 15%. The method was successfully applied to investigate the pharmacokinetics of DHA from five healthy subjects, although carry over and the role of anticoagulants were not tested.Conclusion: The LC-MS/MS assay for the quantification of plasma DHA was validated for selectivity, linearity, lower limit of quantitation, accuracy, precision, matrix effect and stability. Although clinical applicability was demonstrated, this method was to be improved to address the not-tested validation parameters.Keywords: dihydroartemisinin, liquid chromatography/tandem mass spectrometry assay (LC-MS/MS), malaria, Indonesia

Escherichia coli and Klebsiella pneumonia as the Most Common Bacteria Causing Catheter Associated Urinary Tract Infection

Background: Healthcare-Associated Infections (HAIs) are the result of a reaction between taint agents that infected the patient when the patient is hospitalized. A Study from The Center for Disease Control and Prevention shows that most HAIs in hospital are urinary tract infection, most of the infection incident in patient are caused by catheter. Catheter indwelling is notable in medical sphere. This study aimed to inquire case number of Catheter-Associated Urinary Tract Infection (CAUTI) in Dr. Soetomo General Hospital, the feature of CAUTI patients, the type of bacteria that cause CAUTI, and what is the relation among sex and bacteria colony.Materials and Methods: An analytic observational study with the population of pediatric hospitalized patients of Dr. Soetomo General Hospital was conducted in January-December 2017. Samples collected were positive urine culture from pediatric hospitalized patients. Information regarding the bacteria that cause CAUTI, gender, and length of catheter usage were collected.Results: There were total 140 samples of positive urine culture in pediatric patient, and 38.5% was diagnosed as CAUTI. Overall CAUTI was often found in male subjects (51.9 %), and similar with ≤1-year old patients which also often found in male subjects (60.8%). The highest length of catheter usage was 3-5 days (42.5%). All subjects had fever as a clinical sign and 83.3% had suprapubic pain. Escherichia coli and Klebsiella pneumoniae infections were highly discovered. There was an association between gender and urine culture colony count (p=0.02).Conclusion: CAUTI is commonnly found in Dr. Soetomo General Hospital, and two bacteria that cause the most infection were E. coli and K. pneumoniae.Keywords: catheter, urinary tract infection, healthcare associated infection

Innate Immune Response to House Dust Mite Allergens in Allergic Asthma

Asthma is a major health problem and one of the leading causes of death in the world. The prevalence of asthma in Indonesia is high, with a recurrence >50%. Allergic sensitization in asthma is mainly caused by house dust mite (HDM) allergens, both from the mite’s body and its contaminants (e.g., lipopolysaccharides). HDM allergens stimulate several pathways in the innate immune response based on the HDM allergen groups that sensitize them. The innate immune response to HDM allergen exposure occurs when pattern recognition receptors (PRRs) recognizes the allergen, thereby stimulating respiratory epithelial cells to release cytokines, namely, thymic stromal lymphopoietin (TSLP), interleukin-25 (IL -25), and IL-33. The release of IL-25 and IL-33 activates group 2 innate lymphoid cells (ILC2) to release Th2-type cytokines (i.e., IL-5 and IL-13), resulting in allergic airway inflammation via IgE secretion by B cells, recruitment of eosinophils, and respiratory tract remodeling. Dendritic cells induce an adaptive immune response through Th2 activation in the sensitization and effector phases. Other mediators that contributed to the innate immune response include C-C motif chemokine ligand 20 (CCL-20) and granulocyte-macrophage colony-stimulating factor (GM-CSF). A deeper understanding of the components and mechanisms involved in innate immunity against HDM allergens creates the potential to develop alternative therapeutic targets for allergic asthma treatment.Keywords: house dust mite allergens, innate immunity, allergic asthma, respiratory epithelium, inflammatory cytokines

The Stem Infusate and Ethanol Extract of Physalis angulata Inhibitory Activities against a-Glucosidase and Xanthine Oxidase

Background: Infusate of the whole plant of Physalis angulata is used traditionally for the remedy of various diseases including diabetes and gout. This study focused on the stem of P. angulata. The objectives of this study were to investigate the potential of the stem infusate (INPA) and ethanol extract (EEPA) of P. angulata as inhibitors of α-glucosidase and xanthine oxidase.Materials and Methods: INPA and EEPA were determined for their α-glucosidase and xanthine oxidase inhibition activities in vitro, whereas antioxidant activity was determined by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay. Reference inhibitors were used for comparison. The total phenolic compounds were also estimated.Results: EEPA had more concentrated phenolic than INPA which were 7.96 and 0.08 mgGAE/g dried biomass, respectively. INPA and EEPA inhibited α-glucosidase considerably, with IC50 of 149.11 and 409.86 µg/mL, respectively (acarbose was 130.66 µg/mL). However, they inhibited xanthine oxidase weakly, with IC50 of 0.546 and 2.643 mg/mL, respectively, compared with allopurinol 0.005 mg/mL. EEPA scavenged DPPH radicals very weakly (16.04 mg/mL) compared to BHT (0.021 mg/mL), whereas no activity was observed for INPA.Conclusion: The stem infusate and ethanol extract of P. angulata are able to inhibit the activity of α-glucosidase, thus can be further explored for sources of bioactive compounds with α-glucosidase inhibition activity.Keywords: α-glucosidase, infusate, ethanol extract, Physalis angulata, stem, xanthine oxidase

Low Total Lymphocyte Count as the Risk of Hospital Acquired Malnutrition in Children

Background: Hospital Acquired Malnutrition (HAM) is characterized by inadequate nutritional therapy and the risk of developing malnutrition during the hospital stay. In clinical practice, there are many measurements to determine nutritional status. Total lymphocyte count (TLC) is associated with impaired function of immune system in malnutrition. The purpose of this study was to evaluate the prognostic value of TLC to the occurrence of HAM in pediatric patients.Materials and Methods: This an observational study with a prospective cohort design. Subjects were assessed for weight at the first day of hospitalization, then the subjects were followed until they were discharged. Body weight was re-measured on discharge to determine the presence or absence of HAM. This research was conducted at Sanglah Hospital from May-December 2019. Subjects who met the inclusion and exclusion criteria were enrolled in the study.Results: Among 120 subjects, 55 subjects or 45.8% were malnourished on admission. Subjects with a low TLC compared to a normal TLC had a 3.9-fold risk of experiencing hospital acquired malnutrition (95% Confidence Interval: 1.59 to 7.19, p=0.001). Subjects who had a low TLC had HAM of 61.8%, while subjects who had a normal TLC had HAM of 32.3%. In multivariate analysis, low TLC was the only risk factor for HAM in this research.Conclusion: This study proved that low TLC is the risk of HAM. Total lymphocyte count could be used as predictor of the risk of HAM in hospitalization children.Keywords: hospital malnutrition, total lymphocyte, children

Cancer Genetics and Epigenetics in Cancer Risk Assesment

Compared to the normal tissues, cancer cells tend to have higher proliferation rate and often lost their ability to undergo apoptosis. In addition, cancer cells can separate themselves from their original tissue thus causing metastasis in other part of body. While undergoing program cell death, disordered cellular programming can happen. The main causes of this cellular programming anomaly are epigenetic and genetic alterations, which have been known as two separate mechanisms in carcinogenetic. A recent outcome of whole exome sequencing of thousands of human cancers has been the unexpected discovery of many inactivating mutations in genes that control the epigenome. These mutations have the potential to disturb the DNA methylation patterns, histone modifications, and nucleosome positioning, hence, the causing gene expression alternation. Genetic alteration of the epigenome therefore contributes to cancer just as epigenetic process can cause point mutations and disable DNA repair functions. Epigenetic mechanisms changes could cause genetic mutations, and genetic mutations in epigenetic regulators could cause epigenome changes. Knowing that epigenome play a major role in the hierarchy of gene control mechanisms suggests that mutations might have impact on multiple pathways related to cancer phenotype. This pinpoint the fact that recently, the way the genes are organized and controlled are suggested to be a relevant factor for human carcinogenesis.Keywords: cancer genetic, cancer epigenetic, oncogens, tumor suppressor genes, driver mutation, passenger mutation

Healing the Fundamental Unit of Heredity (Gene Therapy): Current Perspective and What the Future Holds

The ability to make precise adjustments to the human genome has been a goal of healing in which gene also introduces as the fundamental unit of heredity, in biomolecular technology in genetic diseases have opened new knowledge such as gene therapy. Gene therapy is a technique to repair DNA where its usage is to treat the malignancy and inherited genetic diseases. Gene therapy is a choice to the genetic cloth that goals to remedy a sickness this is hard to deal with or perhaps has no treatment. Currently, gene remedy is done in approaches to patients, specifically embryonic cells and somatic cells, every in vivo and ex vivo. Moral considerations with modification of the difficulty's cells and oversight of regulation and reagents want to be taken into consideration within the gene therapy project. Applications for using gene remedies have begun to be widely used, which include in case of maximum cancers, coronary heart disorder, infectious sicknesses, and others. Gene therapy has spread to a wide range of applications then go beyond the modification of genetic disorders. Advances in genetic modification of cancer cells and immunity and the use of viruses and bacteria to control cancer cells have resulted in many clinical trials and product developments for cancer treatment. The miracles and blessings of gene therapy are might believe, but even though they are being studied and developed now and, in the future, so that the desire for gene therapy may be even better future.Keywords: gene therapy, genetic recombination, gene therapy application

Choline-deficient High-fat Diet-induced Steatohepatitis in BALB/c Mice

Background: Non-alcoholic steatohepatitis (NASH) is an expanding cause of chronic liver disease worldwide, including Indonesia, with higher risk progression to cirrhosis and hepatocellular carcinoma. Preclinical experiments using several mice models have been conducted to clarify its complex pathogenesis. This study was designed to investigate whether BALB/c mice on a choline-deficient high-fat diet can be used as a model for NASH. Materials and Methods: BALB/c male mice were fed choline-deficient L-amino acid-defined high-fat diet (CDAHFD) or a standard diet for six weeks. The body and liver weights, liver histology, and plasma biochemistry were analyzed. The relative expression levels of tumor necrosis factor (TNF)α, transforming growth factor (TGF)β1, collagen-1α1 (COL1α1), glutathione peroxidase 1 (GPx1), and uncoupling protein 2 (UCP2) genes in the livers were analyzed using a two-step real time-polymerase chain reaction. Liver fatty acids composition was analyzed using gas chromatography with flame ionization detector (GC-FID). Results: CDAHFD induced steatohepatitis in BALB/c mice with increased plasma levels of alanine aminotransferase. The liver of CDAHFD-fed BALB/c mice showed upregulated relative expression levels of TNFα, TGFβ1, COL1α1, GPx1, and UCP2 genes. The liver fatty acid analysis showed a significant accumulation of saturated fatty acids (SFAs) and an increased ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) in the livers of CDAHFD-fed BALB/c mice. Conclusion: This study suggests that CDAHFD can induce steatohepatitis in BALB/c mice and therefore may be used as NASH mice model.Keywords: steatohepatitis, fatty liver, choline-deficient high fat diet, BALB/c