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Gede Pardianto,1 Nila Moeloek,2 Julia Reveny,1 Sutarman Wage,1 Imsyah Satari,3 Rosita Sembiring,1 Nuttamon Srisamran4,5 1Sumatera Utara University, Medan, 2University of Indonesia, Jakarta, 3Sumatera Eye Center, Medan, Indonesia; 4Thammasat University, Pathum Thani, Thailand; 5The World Medical Center, Nonthaburi, Thailand Purpose: To determine the effect of phacoemulsification on macular volume and thickness using spectral domain optical coherence tomography examinations. Methods: Twenty-seven eyes of 27 subjects who underwent phacoemulsification were studied. All nine areas of the macula were examined by spectral domain optical coherence tomography preoperatively and 2 months postoperatively. Effective phacoemulsification time and absolute phacoemulsification time were also recorded. Results: There were statistically significant differences in macular thickness between preoperative and postoperative spectral domain optical coherence tomography examinations in nine areas including macular volume. In the paracentral macular area, the thickness of three quadrants significantly increased (superior P=0.015; temporal P=0.001; and nasal P=0.023). Peripheral macular thickness also increased significantly in the superior (P=0.05) and temporal macular areas (P0.05), but a significant correlation (P=0.011) was found between absolute phacoemulsification time and change in macular volume. Conclusion: Macular thickness changes in the nasal, superior, and temporal quadrants of the paracentral area and the superior and temporal quadrants of the peripheral area, as well as macular volume, may be used as detailed biomarkers to measure the effects of intraocular pressure fluctuations and maneuvers in phacoemulsification intraocular surgeries. Keywords: phacoemulsification, effective phaco time, absolute phaco time, SD-OCT, macula

Chronic Liver Disease (CLD) is associated with hepatocyte damage, massive inflammation and liver fibrosis, capable of promoting cancer. Although, majority of hepatocytes diminished in CLD, stem cell derived from circulating endogenous Mesenchymal Stem Cells (MSCs) plays several roles in the rapid regeneration process, through regulating serum Platelet Derived Growth Factor-β (PDGF-β) levels. The aim of this study was to analyze the effect of MSCs administration in the liver fibrosis of rats by measuring their serum PDGF-β level and histopatology appearance. MSCs was isolated from Sprague Dawley (SD) rats and the liver fibrosis induced with carbon tetrachloride (CCl4). In addition, MSCs (1 x 106 cells) were intravenously injected 24 h after CCl4 with the Serum PDGF-β level determined by enzyme linked immunosorbent assay (ELISA) on day 3 and 14 after intravenous administration. Hematoxylin and eosin (H&E) staining was used to evaluate histopatology, while statistical analysis was performed with SPSS version 12.0. The obtained data were analyzed by one-way ANOVA with a LSD comparison post hoc test. MSCs treatment significantly increased serum PDGF-β level compared with the control group on day 3 ( p < 0.05), which was significantly reduced liver fibrosis on histopatology appearance on day 14 ( p < 0.01). Our study indicates that MSCs alleviate liver fibrosis through the PDGF-β regulation in rats. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) remains a significant global health concern with considerable high morbidity and mortality and its development is influenced by various genetic and environmental factors. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a vital regulator of low-density lipoprotein receptor (LDLR) metabolism, directly impacting serum cholesterol levels. However, its role in development of CAD is not fully understood. The aim of this study was to assess the association between the level of PCSK9 and coronary lesion severity in patients with CAD. A case-control study using consecutive sampling was conducted among CAD patients at H. Adam Malik General Hospital and Murni Teguh Memorial Hospital, Medan, Indonesia. A total of 200 CAD patients were divided into two groups based on the SYNTAX score: control (score ≤22, n=100) and case (score >22, n=100). Plasma PCSK9 levels were measured from venous blood using quantitative sandwich enzyme immunoassay. The Chi-squared test was used to analyze the data. Our data suggested that PCSK9 level was associated with coronary lesion severity ( p <0.001) of which high PCSK9 level was associated with severe coronary lesion. We also found that hypertension ( p <0.001), smoking ( p =0.072), diabetes ( p <0.001), dyslipidemia ( p <0.001), obesity ( p =0.023), and family history ( p =0.001) were associated with lesion severity. Using the receiver operating characteristic (ROC) curve analysis, the cut-off 70.35 ng/mL of PCSK9 had sensitivity 75% and specificity 78% to predict severe coronary lesion. This study highlights that PCSK9 level has moderate sensitivity and specificity to predict the coronary lesion severity among CAD patients., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 The Author(s).)

Aim Allergic rhinitis (AR) is a heterogeneous condition that has been associated with inflammatory responses and is characterized by clinical typical symptoms of nasal itching, sneezing, watery discharge and congestion. Mesenchymal stem cells (MSCs) are multipotent stem cells that have the immunoregulatory ability by secreting various cytokines which potent as a promising therapeutic modality for allergic airway diseases, including AR. The aim of this study was to investigate the effect of rat UC-MSCs on the number of mast cells, the expression of Hsp70 indicated by the nasal symptoms allergic, particularly nasal rubbing in ovalbumininduced AR rats. Methods Fifteen male Wistar rats (6 to 8 weeks old) were randomly divided into three groups (control group, sham group, and OVA+MSCs group). OVA nasal challenge was conducted daily from day 15 to 21, and UC-MSCs (1x10 6 ) were administrated intraperitoneally to OVA-sensitized rats on day 21. Nasal rubbing was observed from day 22 to 28. The rats were sacrificed on day 22 and day 28. The nasal cavity tissues were prepared for histological observations. Results The administration of UC-MSCs could reduce the number of mast cells and the expression of Hsp70 leading to reduction of nasal symptoms allergic, particularly nasal rubbing. Conclusion Based on this finding, MSCs present a promising immediate curative effect to the inflammatory reaction in AR rats., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Background and Objective: Thymoma is a rare malignant tumor that usually with an indolent presentation, which was falsely assumed to be benign previously. The tumor suppressor P53 (TP53) and EGFR gene mutate most frequently in human cancers. We tried to investigate the presence of TP53 and EGFR mutations among thymoma patients referred to an Indonesian referral respiratory hospital and to discuss its potential role in thymoma management and prognosis., Material and Methods: Surgically resected tumor tissues were collected from thymoma patients and then underwent genomic analysis. PCR was performed on the extracted Paraffinized  DNA to amplify exon 6 of TP53 and exons 18, 19, and 21 of EGFR. The evaluation of mutational status was done using direct sequencing and sequence analysis of purified PCR products., Results: Among 27 collected samples, TP53 exon 6 mutation, namely  missense mutation and nonsense mutation, was observed in two samples (7.4%). EGFR exon 18 mutation, namely E709K and nonsense mutation, was found in 2 samples (7.4%). An intronic mutation in EGFR exon 19 (3.7%) and exon 21 (3.7%) was observed in one sample., Conclusion: TP53 and EGFR mutations were not most frequent, so it seems that these genes are not involved in the pathogenesis of thymoma in Indonesian patients. Nevertheless, we found two samples with a significant mutation in p53 and EGFR genes, suggesting further research on thymoma prognostification and targeted therapy.

Aim To investigate the effect of umbilical cord-derived mesenchymal stem cells (UC-MSCs) administration among liver fibrosis experimental rat model via the regulation of angiotensin II type 1 receptor (AT1R) and platelet-derived growth factor-β (PDGF-β) due to their therapeutic potential to replace liver transplantation for advanced liver fibrosis. Yet the mechanism of action has been questionably associated with UC-MSCs fibrosis regression properties. Methods Sprague-Dawley (SD) rats (n=18) were separated into three groups (control, untreated liver fibrosis, and UC-MSCs treated group). Serum PDGF-β level was determined by enzymelinked immunosorbent assay (ELISA) following 14 days of UCMSCs injection. Meanwhile, AT1R expression was interpreted based on immunoreactive score (IRS) stained using polyclonal antibody and liver fibrosis stained with hematoxylin & eosin was graded using the METAVIR score. Results UC-MSCs were isolated successfully from rat umbilical cord. Liver fibrosis was observed following 14 weeks of CCl4 injection concurrent with higher serum level of PDGF-β, but the UC-MSCs-treated group had lower level (980.08 ±289.41 and 606.42±109.85 for untreated liver fibrosis and UC-MSCs treated group, respectively; p=0.004). There was also a high expression of AT1R among untreated liver fibrosis group, as well as highgrade liver fibrosis versus localized fibrosis and low level of AT1R expression among UC-MSCs treated-group (p=0.001). Conclusion UC-MSCs administration could ameliorate liver fibrosis by reducing the AT1R expression and PDGF-β serum levels, and intervention through this signaling pathway could be alternative evidence for the causative of positive outcome., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Aim Accumulated evidence suggests that vitamin A and D agonists can alleviate the development of atherosclerosis. Therefore, the aim of this study was to determine the effect of vitamin A and D combination supplement on interleukin-1β (IL-1β) and clinical outcome in ischemic stroke. Methods A single-blind, randomized controlled trial was conducted on ischemic stroke patients at Adam Malik Hospital between March 2018 to February 2019. The patients were randomized into 4 groups of the treatment consisting of supplementation using vitamin A or D only, combination of vitamin A and D, and placebo group, all given for 12 weeks. Clinical outcome was determined using the National Institute of Health Stroke Scale (NIHSS). At the time of admission and after the treatment was completed, all patients were measured for vitamin A, vitamin D, and IL-1β serum level, and NIHSS score. Results From the total of 120 patients, in the combination group there were significant increments on both vitamin A (p=0.04) and vitamin D (p=0.01) serum level after 12 weeks of the treatment, compared to the other groups. In conjunction, IL-1β serum level showed a significant decrement in the combination group (p<0.001). Lastly, the biggest improvement of NIHSS could be seen in the combination group, which was marked by the highest decrement of NIHSS score (p<0.001). Conclusion Administration of combination of vitamin A and D supplementation can significantly increase vitamin A and D serum level, decrease IL-1β serum level, and ultimately improve clinical outcome in ischemic stroke patients., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Aim Alpha2-Heremans-Schmid glycoprotein (AHSG), a circulating plasma protein, plays an essential role in bone and vascular mineralization. The impact of AHSG gene polymorphisms on aortic calcification in haemodialysis patients was inconsistent. We performed this study to clarify precise association among AHSG gene Thr256Ser single-nucleotide polymorphisms and aortic calcification. Methods Patients on stable regular haemodialysis treatment for more than thirty months were included in a cross-sectional study at Rasyida Renal Hospital Medan. Lateral spine X-rays were performed to evaluate the aortic calcification. Genotyping for the polymorphisms was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. Results Aortic calcification was detected in 69.8% of patients. From 106 patients, 49 patients (46.2 %) had CC (Thr/Thr), 54 (51.0%) had CG (Thr/Ser) and three (2.8%) patients had GG (Ser/ Ser) polymorphism. The proportion of patients with heterozygous or homozygous G allele (CG and GG genotypes) is more likely (91.2%) to have aortic calcification. The bivariate analysis showed that Thr256Ser polymorphism (G allele) was associated with increased risk for aortic calcification (PR=2.03; 95% CI 1.48-2.80; p<0.001). However, overall results from multivariate analysis showed that Fetuin-A level <204 pg/mL (PR=22.0; 95% CI 3.32-145.91; p=0.001) and IL-6 level ≥53.05 mg/dL (PR=19.50; 95% CI 2.87-132.41; p=0.002) were the major risk factors for the occurrence of aortic calcification. Conclusion AHSG Thr256Ser gene polymorphism showed an association with aortic calcification in regular haemodialysis patients, but Fetuin-A and IL-6 have a dominant role in the development of aortic calcification., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Cutaneous Squamous Cell Carcinoma (cSCC) is a malignant keratinocyte tumour that develops through the suprabasal epidermis. This malignant tumour is the second most common skin malignancy after Basal Cell Carcinoma (BCC). The increased incidence of cSCC is directly proportional to increasing age. Generally, the predisposing factor of cSCC is exposure to recurrent sunlight for a long time, so localisation of cSCC is a part of the body that often exposed to direct sunlight, such as the forehead, face, ears, scalp, neck, and back of the hand. The carcinogenesis process of cSCC is a cumulation of a series of events, one of which plays an important role is the proliferation index assessed by Ki-67. Forty-eight tissue paraffin blocks were diagnosed histopathologically as cutaneous squamous cell carcinoma from the Anatomical Pathology Laboratory of the Faculty of Medicine, Universitas Sumatera Utara and the Anatomical Pathology Unit of Haji Adam Malik General Hospital Medan, as the research sample. The results of protein expression from Ki-67 were assessed based on area. There was no significant correlation between cSCC grading and Ki-67 expression (p > 0.05). Ki-67 antigen tumour marker, widely used to determine the level of tumour cell proliferation., (Copyright: © 2019 Ibnu T. Alferraly, D. Munir, I. B. Putra, R. J. Sembiring.)

Background: Some of the excitatory neurotransmitters including glutamate have been suggested to be involved in headache pathophysiology. To our knowledge, there is a lack of publication about flunarizine efficacy in chronic tension-type headache (CTTH) treatments and the roles of glutamate in CTTH pathophysiology., Aim: This study aimed to investigate the flunarizine effect on serum levels of glutamate and its correlation with headache intensity based on the Numeric Rating Scale for pain (NRS) scores in CTTH patients., Method: In a prospective randomised, double-blind study with pre and post-test design, seventy-three CTTH patients were randomly allocated with flunarizine 5 mg, flunarizine 10 mg and amitriptyline 12.5 mg groups. The serum levels of glutamate and NRS scores were measured before and after 15-day treatment., Results: Flunarizine 5 mg was more effective than flunarizine 10 mg and amitriptyline 12.5 mg in reducing serum glutamate levels, whereas amitriptyline 12.5 mg was the most effective in reducing headache intensity. There was found nonsignificant, but very weak negative correlation between headache intensity and serum glutamate levels after flunarizine 5 mg administration (r = -0.062; P = 0.385), nonsignificant very weak negative correlation after flunarizine 10 mg administration (r = -0.007; P = 0.488) and there was found a significant moderate positive correlation (r = 0.508; P = 0.007) between headache intensity and serum glutamate levels after amitriptyline 12.5 mg administration., Conclusion: Since there was no significant correlation found between serum glutamate and headache intensity after treatment with flunarizine, it is suggested that decreasing of headache intensity after flunarizine treatment occurred not through glutamate pathways in CTTH patients.

Purpose: We sought to evaluate prevalence, age-adjusted distribution, and impact of single and multiple high- and low-risk human papillomavirus (HPV) subtypes and their associations with cervical lesions., Methods: Data were extracted from 11,224 women who underwent routine screening of HPV genotyping and liquid-based cytology co-testing. Fifteen high-risk (HR) and six low-risk (LR) HPV types were genotyped., Results: Overall HPV prevalence was 10.7 %, and young women (under 21 years old) harbored highest HPV infection rate (40.38 %). The rate declined in old women 9.49 % (age 30-49) and 6.89 % (age 50 and above). Normal cytology had lowest HPV (5.66 %) compared to low-grade (60.49 %), high-grade (71.96 %) squamous intraepithelial lesions (LSIL and HSIL) and squamous cell carcinoma SCC (86.9 %). LR HPV subtypes were absent in SCC and were consistently lower than HR HPV in LSIL (6.74 vs. 33.54 %) and HSIL (2.12 vs. 51.32 %). Multiple HPV infection was more frequent in young women under 30 years old (10 %) than older women (2 %) and in LSIL (20.2 %), HSIL (18.5 %) than SCC (4.4 %). HR HPV 52, 16, 18, and 58 were the most frequent subtypes in normal, LSIL, and HSIL. Greater or equal proportion of HPV 16, 18, 45, and 52 was found in SCC compared to normal cytology (SCC/normal ratios 4.8, 1.2, 1.6, and 1.7). While important in LSIL and HSIL, HPV58 was not detected in SCC., Conclusion: Taken together, identification of these HPV types, especially HPV 16, 18, 45, and 52, and their associated cervical lesions may improve cervical cancer preventive strategies in Indonesia.