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BACKGROUND: Histopathological examination is the gold standard for diagnosing meningioma and determining the treatments. However, it is invasive in nature. This study was conducted to identify intratumoral and peritumoral apparent diffusion coefficient (ADC) value and mRNA O6-methylguanine-DNA methyltransferase (MGMT) expression in meningioma. METHODS: Data were collected from 39 patients who were clinically diagnosed with meningioma. However, only 37 patients met the inclusion criteria. These subjects then underwent examinations and received treatment from October 2017 to September 2018. Magnetic resonance imaging (MRI) data with diffusion-weighted imaging-apparent diffusion coefficient (DWI-ADC) sequence, histopathological diagnosis of meningioma, and results of MGMT mRNA expression were obtained. RESULTS: The most frequent type of low-grade and overall tumor was meningioma not otherwise specified (56.8%). For high-grade tumor, there were two atypical cases: atypical meningioma (2.7%) and rhabdoid meningioma (2.7%). Meningothelial meningioma had the highest mean value of minimum intratumoral ADC at 864.57±219 x10-3 mm2/s, whereas rhabdoid meningioma had the lowest at 417 x10-3 mm2/s. For minimum peritumoral ADC, rhabdoid meningioma had the highest mean value at 1,651 x10-3 mm2/s, while atypical meningioma has the lowest at 1,281 x10-3 mm2/s. For MGMT mRNA, meningothelial meningioma had the highest mean value at 10±1.2 fold change, whereas rhabdoid meningioma had the lowest mean at 6.18 fold change. CONCLUSION: WHO grade I meningiomas had higher minimum intratumoral ADC values and higher MGMT mRNA expression than the high-grade tumors. Minimum peritumoral ADC values differed across the histopathological grades. KEYWORDS: meningioma, RNA, messenger, MRI, methyltransferases, RT-PCR, ADC, MGMT mRNA

Background Traumatic brain injury is a dangerous life threatening condition. This study examines the role of MLC901 in increasing neurogenesis. The aim of this study was to demonstrate the role of MLC901 in increasing neuron cell (neurogenesis) in rat with traumatic brain injury using the synaptophysin marker. Methods The synaptophysin levels were measured as a marker for neuron cell (neurogenesis) of brain nerve cells in Sprague-Dawley rats aged 10–12 weeks, weighing 200–300 g. All rats (n = 10) were performed as traumatic brain injury using The Modified Marmourou Model, then they were divided into 2 group, one group was given MLC901 (n = 5) and the other group was not given MLC901 (n = 5). The synaptophysin levels in both groups were assessed after 6 weeks and also carried out an examination of immnuhistochemical from the brain tissue of both groups. Results There was an increase in the number of neuron cells as evidenced by synaptophysin ihc staining in the rats given MLC 901 (Neuroaid II) compared to those without MLC 901. Synaptophysin levels were lower in the control group than in the MLC 901 group (81.6, SD: 13.52 vs 118.4, SD: 12.198, p = 0.062). Conclusion These research suggest that MLC901 can increase neurogenesis in traumatic brain injury and also appeared as synaptophysin antibody that binding to cytoplasm of neuronal cells in the rat brain., Highlights • Experimental study on rats with traumatic brain injury to determine the role of MLC 901 in increasing number of neuronal cells (neurogenesis) in rat with traumatic brain injury using the synaptophysin marker. • The synaptophysin levels in both groups were assessed after 6 weeks and also carried out an examination of immnuhistochemical from the brain tissue of both groups. • There was an increase in synaptophysin levels in the rats given MLC 901. • MLC 901 can increase neurogenesis in traumatic brain injury.

BACKGROUND: Some of colorectal cancers (CRCs) are familial, however, heterozygote relatives have approximately 80% lifetime risk of cancer. Risk assessment of CRC’s family could be calculated by direct measurement of mRNA gene expression and Bayesian theorem which is modifying initial background of pedigree risk with additional conditional information. This application has not been reported. METHODS: The cross-sectional translational sequential studies were performed: (1) adenomatous polyposis coli (APC) and MutS homolog (MSH)2 mRNA quantitative RT PCR gene expressions in tissue and whole blood CRC patients; (2) gene expression was determined in matched controls; and (3) pedigree and Bayesian analysis was calculated in the patient’s family of Proband. RESULTS: Fourty CRC and 31 control subjects were enrolled. The mean blood APC level control’s group was 13,261±670 fold-change (fc) and blood MSH2 level was 12,219±756 fc. The cut-off points for hereditary APC was 12,195 fc and MSH2 was 11,059 fc. The mean APC blood level in CRC subject was 11,578±2,638 fc and MSH2 blood level was 11,411±2,912 fc. There were significant differences APC and MSH level between tissue and blood level in CRC. Eight of 40 CRC subjects had a history of familial CRC. Four patients and 10 Probands were available for recurrence risk evaluation of pedigree analysis, RNA PCR quantitative and Bayesian calculation. CONCLUSION: There was determined a cut-off point of hereditary mRNA quantitative expression. The APC and MSH2 levels in CRC subjects were significantly lower than controls. Bayesian analysis allowed for the calculation of relative risk in CRC family members and considered in clinical practice. KEYWORDS: hereditary CRC, APC gene, MSH gene, Bayesian analysis

Background The ability of Mycobacterium tuberculosis to survive intracellularly, provides a cellular adaptive immune response played by specific T cells to defend against tuberculosis. The adaptive immune response to Bacillus of Calmette and Guerin (BCG) immunization is responded to by B cells, T Follicular B helper, T regulatory, restriction CD1, CD8+, CD4+, Th1, Th2, and Th17. BCG immunization can cause a tuberculin test reaction to being positive. The tuberculin test is a method for diagnosing TB infection and for screening individuals for latent infection and assessing the rate of TB infection in a given population. Methods a nested case-control survey was conducted on patients with a diagnosis of TB and parents 0–18 years of age from 3 hospitals in Indonesia during September–November 2019 with a total sample of 69 people undergoing clinical examinations, supporting and diagnosing subjects, blood sampling 1–2 cc for examination mRNA gene Treg, Treg, CD 4+, and CD 8+, then centrifuged at 3000 rpm for 10 min to support blood cells and serum. Results There was a significant relationship between expression of mRNA gene Treg with TST (p = 0,000), Treg with TST (p = 0,000), and CD4+ with TST (p = 0,000). Meanwhile, CD8 + was not significantly associated with TST (p = 0.118). Conclusions It is necessary to check the expression of mRNA gene Treg, Treg, CD4+, and CD8+ with more samples to find the mean value that shows the protective value of further TB., Highlights • The Mantoux tuberculin skin test (TST) is one of the criteria to determine whether a person is infected with Mycobacterium tuberculosis. It is often used to screen individuals for latent infection and assess rates of TB infection in a given population. tuberculin test results with induration diameter> 10 mm were positive regardless of the cause. Patients in this study were children who had been vaccinated against BCG and diagnosed with TB in their early toddler years. It was necessary to see the adaptive immune response that existed when the child was infected with TB. • The main immune response that acts as protection against TB is played by cellular immunity, namely CD4 and CD8 T cells. We thought that if we could find between TST and adaptive immune response, TST could be a prior test to determine prognosis or disease progression. • We found a strong correlation between immune activation and Treg cell frequency in TST positive persons. A higher Treg consentration was found in TST positive subjects. Nevertheless, local immune responses may differ from those in peripheral blood and exploring this interaction in the site of active infection will give important clues about their involvement in protection or pathogenesis . According to our studies the increased Treg cell frequency observed in the blood of people with active tuberculosis is likely a response to inflammation and bacterial burden.

Introduction Ischemia-Reperfusion Injury (IRI) is a complication following the reperfusion of ischemic tissues; it requires immediate treatment, as it can lead to severe infection and tissue death. The purpose of this study was to demonstrate the ability of Hyperbaric Oxygen Therapy (HBOT) to treat SIRS (Systemic Inflammatory Response Syndrome) caused by IRI and to provide long-term functional assessment for a period of up to 5 years. Case presentation Two cases of avulsions of the hand at the levels of the wrist joint and the medial third forearm, severed by machetes. Both patients were male and in their twenties. Hand replantation was carried out after 30 minutes (medial third forearm case) and 11 hours (wrist joint case) of ischemic time. A couple of days after surgery, both patients experienced SIRS as a result of IRI. The patients were brought to the hyperbaric chamber and received 3 consecutive 90-min sessions of HBOT at 2.4 ATA 3 days in a row. The outcomes were compared in a table with each patient's vital signs and laboratory results, both before and after HBOT. A significant improvement was seen at the follow-ups in vital signs and laboratory results for both patients after HBOT administration. Long-term follow-up also showed satisfying results for hand function, proven by low DASH (Disabilities of the Arm, Shoulder, and Hand) scores. Conclusion HBOT was able to treat SIRS in both patients. Favorable long-term hand function results signify successful extremity replantation., Highlights • Ischemia-Reperfusion Injury (IRI) is a complication following the reperfusion of ischemic tissues. • Two cases of avulsions of the hand that had underwent hand replantation had experienced systemic inflammatory response syndrome (SIRS) due to IRI. • Administration of HBOT has been proven to be an effective treatment for post-hand replantation SIRS.

Objective Glioma is one of the most frequent and disabling primary brain tumour. Patients are not only dealing with survival, but also quality of life, which remains another major concern. Karnofsky Performance Scale (KPS) is one of the most commonly used scale to assess patients' quality of life. A recent scale, known as Neurological Assessment of Neuro-Oncology Scale, has surfaced to examine neurological disability caused by brain tumour. Previous study showed this scale to be superior to KPS in predicting survival. However, these scales have never been used to foresee functional scale improvement during disease progression. We sought to determine whether initial KPS and NANO Scale can predict functional scale improvement 2 months after surgery. Methods Patients with glioma grade II-IV were included in the study. IDH mutation and MGMT methylation were tested. KPS and NANO scale were examined before surgery and 2 months after surgery. Favorable outcome (FO) was defined as improvement in functional scale 2 months after surgery. Patients initial functional scales were analyzed towards favorable outcome. Results Glioma WHO grade II, III and IV was found in 17 patients (36.2%), 3 patients (6.4%) and 27 patients (57.4%) respectively. Median KPS before and 2 months after surgery were 50 (30-80) and 60 (0-100), whereas median NANO scale before and 2 months after surgery were 5 (0-12) and 3 (0-12). Favorable outcome was found in 63.8% (KPS) and 78.7% (NANO Scale). Patients initial functional scales were significantly related to FO. Conclusion Good initial functional scales are 4 to 5 times likely of having a favorable outcome 2 months after surgery.

Introduction The central nervous system (CNS) is the most metabolically active organ characterized by high oxygen demand and relatively low anti-oxidative activity, which makes neurons and glia highly susceptible to damage by reactive oxygen and nitrogen byproducts as well as neurodegeneration. Free radicals are associated with secondary injuries that occur after a primary brain injury. Some of these free radical products include F2-Isoprostane (F2-IsoPs), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE) and acrolein. Methods In this study we measured serum F2-IsoPs levels as markers of free radical activity in 10–12 week-old male Sprague-Dawley rats weighing 200–300 g, all rats (n = 10) subjected with a head injury according to the modified marmourou model, then divided into 2 groups, one group treated with CAPE (Caffeic Acid Phenethyl Ester) (n = 5) and the other not treated with CAPE (n = 5), serum levels in the two groups were compared starting from day-0 (before brain injury), day-4 and day-7. Results We found lower F2-IsoPs levels in the group that received the CAPE treatment compared to the group that did not receive the CAPE treatment. Conclusion CAPE is capable of significantly reducing oxidative stress in brain injury., Highlights • The central nervous system (CNS) is the most metabolically active organ characterized by high oxygen demand and relatively low anti-oxidative activity. • Free radicals are associated with secondary injuries that occur after a primary brain injury. • Caffeic Acid Phenethyl Ester (CAPE) administration in a rat model with brain injury can reduce the formation of F2-Isoprostane (F2-IsoPs) as an indicator of oxidative stress in blood serum post-trauma.

Introduction Peripheral leukocytes can worsen brain damage due to the release of cytotoxic mediators that interfere the blood brain barrier function. One of the oxidants released by activation leukocyte is hypochlorite acid (HOCl) which is formed through the myeloperoxidase (MPO)-H2O2–Cl- system. The neuroprotective effects of an experimental anti-inflammatory drug Caffeic Acid Phenethyl Ester (CAPE) tested in a Traumatic brain injury (TBI) model using Myeloperoxidase (MPO) analysis. Methods This study compares the acute inflammatory response to TBI over time, as measured by MPO activity. Adult Sprague mice were treated for head trauma with marmarou model. At 24 h before trauma, all animals were blood test (n = 10) to examine MPO, then the animal was divided into 2 groups of injured animals treated with CAPE (n = 5), and those not treated with CAPE (n = 5). We used the MPO test to identify the level of polymorphonuclear leukocytes (PMNL) on day 4 and day 7. Results Showed an increase in PMNL infiltration in CAPE untreated animals, this change significantly (P, Highlights • Peripheral leukocytes can worsen brain damage due to the release of cytotoxic mediators that interfere the blood brain barrier function. • One of the oxidants released by activation leukocyte is HOCl which is formed through the MPO-H2O2–Cl-system. • CAPE administration in mice with traumatic brain injury can inhibit the formation of myeloperoxidase as a marker of accumulated neutrophils. • CAPE can reduce Neutrophil serum levels there by preventing brain damage in TBI.

Introduction: Brain tumor is a neoplasm originating from various type of intracranial tissue. Histopathology is the gold standard to diagnose brain tumor. However, due to its invasive nature, the biopsy procedure poses a substantial risk. Therefore, advanced imaging, such as conventional Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS), has been widely developed to determine brain tumor type. Conventional MRI has been a routine examination for a suspected brain tumor in Indonesia, and with the utilization of MRS, could theoretically improve the diagnostic yield. This study aims to find diagnostic properties of conventional MRI, Choline/Creatine and Choline/NAA ratio extracted from MRS, and as a combined parameter to differentiate brain tumor type.Methods: This cross-sectional study involved 52 patients who underwent conventional MRI, MRS, and histopathology examination for a suspected brain tumor. The cut-off from Dean Criteria of conventional MRI, Choline/Creatine and Choline/NAA ratio to classify tumor type was determined from the ROC curve and then the diagnostic parameters were calculated from cross-tabulation. Also, a novel approach was made with logical-mathematical equation (disjunction/ ˅ / “or” and conjunction/ ˄ / “and”) to combined parameter obtained from MRI and MRS to predict histopathological brain tumor type.Results: Conventional MRI combined with MRS improve diagnostic yield compared to a single parameter with a sensitivity of 87.5%, a specificity of 88.6%, accuracy of 88.5%, PPV of 58.3%, NPV of 97.5%, LR+ of 7.68, dan LR- of 0.1.Conclusion: Combination of conventional MRI and MRS parameter could improve the diagnostic yield in differentiating the type of brain tumor.

Background Around 70% of breast cancers (BCs) are estrogen receptor-α (ERα)-positive. Adjuvant endocrine therapy is used to reduce estrogen levels and inhibit signal transduction through the ER. The anti-estrogen drugs that are most commonly used in endocrine therapy belong to the selective ER modulator (SERM) class and include tamoxifen. Although it has been used for three decades in cases of early-stage and ERα-positive BC, resistance to tamoxifen is a common problem. microRNAs (miRNAs) have a potential role in demonstrating BC resistance to tamoxifen therapy. Hence, there is a need to investigate the expression of miRNA-221 (miR-221) in luminal-subtype BC patients receiving tamoxifen therapy. Methods This case-control study investigated luminal-subtype BC patients who had undergone endocrine therapy for at least 1 year. The case group comprised patients with local or metastatic recurrence, and the control group comprised patients without local or metastatic recurrence. Results There was a significant difference in miR-221 expression (p = 0.005) between the case and control groups. There were no significant differences between the groups that were positive and negative for the progesterone receptor (PR) (p = 0.25), had high and low marker of proliferation Ki-67 levels (p = 0.60), were positive and negative for lymphovascular invasion (p = 0.14), and had stage 2 and stage 3 cancer (p = 0.25). Conclusion miR-221 expression was higher in tamoxifen-resistant BC cases. miR-221 is a potential biomarker of tamoxifen resistance., Highlights • Tamoxifen is used to treat early-stage and estrogen receptor-α-positive breast cancer. • Resistance to tamoxifen is a common problem. • Serum microRNA-221 levels were higher in patients with local recurrence and metastasis. • microRNA-221 is a potential serum biomarker of tamoxifen resistance.

The formation of a scar after Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccination influences the effectiveness of protection against Mycobacterium tuberculosis (MTB) infection. The innate immunity plays a critical role both in the pathophysiology of tuberculosis (TB) and BCG vaccination protection mechanism. Parts of innate immunity: macrophages, dendritic cells, and neutrophils, have microbial recognition surface receptors called Toll-like receptors (TLR) 2 and 4. The objective of this study is to compare the serum levels of TLR2 and TLR4 in BCG-vaccinated pediatric patients with pulmonary and extrapulmonary TB. This cross-sectional study included children aged less than 18 years old with contracted TB disease and had received BCG vaccination. The subjects were recruited by convenience sampling from both outpatient and inpatient care at Bhakti Medicare and Jakarta Islamic Hospital, from November 2018 to December 2019. Serum TLR2 and TLR4 levels measured using ELISA of the two groups of subjects: children with pulmonary TB (PTB) and extrapulmonary TB (EPTB), were then compared. The presence of BCG scars was included in the analysis. Independent T-test, ANOVA test, and Kolmogorov-Smirnov normality tests on the SPSS program were used to statistically analyze the results. Serum TLR2 and TLR4 levels were higher in EPTB group, but the difference was not significant (TLR2 p = 0.758 and TLR4 p = 0.646, respectively). Subjects with BCG scars in both groups have significantly higher serum TLR2 and TLR4 levels than those without BCG scars in the EPTB group (EPTB p = 0.001 and p = 0.004, respectively); (PTB p < 0.001 and p < 0.001, respectively). BCG vaccination and MTB infection stimulate better innate immune response in EPTB than in PTB and serum TLR2 and TLR4 levels in those with BCG scars were higher when compared to those without BCG scars.

Introduction and importance Transorbital Penetrating Intracranial Injury (TOPI) is a rare case, but those caused by Wooden Foreign Body are even challenging that may pose unusual diagnostic and surgical challenges. Case presentation we presented a TOPI following a wood penetrated to the left temporal fossa region via orbital roof due to struck the tree branches while got a motor vehicle accident. The patient was fully conscious with decreased visual acuity in the left eye and left ophthalmoplegia. Non-contrast CT scan showed the linear-shaped foreign body, air mimicking that penetrated medial orbit plane to the left temporal fossa. Clinical discussion The surgery was performed with a temporobasal approach and revealed good results with only mild ophthalmologic complications without long-term fatal complications (1-year followed-up). Conclusion early removal of wooden foreign body that penetrates to the intracranial via transorbital is mandatory and should be involved multidisciplinary approach to get the optimal result and avoid the fatal complication both neurologically or ophthalmologically., Highlights • Transorbital Penetrating Intracranial Injury (TOPI) is rare case. • We presented a TOPI following a wood penetrated to the left temporal fossa region via orbital roof due to strucked the tree branches while got a motorvehicle accident. • Early removal of wooden foreign body that penetrate to the intracranial via transorbital is mandatory and should be involved multidisciplinary approach in order to get optimal result and avoid the fatal complication both neurologically or ophtalmologically.

BACKGROUND: The conventional magnetic resonance imaging (cMRI) and apparent diffusion coefficient (ADC) may have a role in predicting tumor grade for gliomas and may in turn assist in identifying tumor biopsy sites. In this study, we aimed to determine the added value of a joint approach of diffusion-weighted imaging (DWI) and cMRI to determine of low grade and high-grade glioma, compare to cMRI alone. METHODS: Data were collected from 56 glioma patients, who underwent examinations and received treatment at Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia, from the period of 2015–2018. Inclusion criteria was patients who underwent cMRI with a DWIADC sequence and patient that were diagnosed with glioma according to the histopathological results. Pathology reports of the imaging results were reviewed independently. A receiver operator curve (ROC) analysis assessed the predictive potential of cMRI and ADC values for low-grade and high-grade gliomas. RESULTS: Fifty-six subjects met the inclusion criteria. The combination of MRI and ADC values increased sensitivity (to 90%) and negative predictive value (to 92.9%), and also improved the negative likelihood ratio (to 0.14). However, the combination of MRI and ADC values had the highest area under the curve (78.6%) and sensitivity (78.6%), which was similar to the separated examination. CONCLUSION: The combination of ADC value and conventional MRI increases sensitivity in differentiating low-grade and high-grade glioma compared to separated examination. KEYWORDS: glioma, conventional MRI, ADC value

Objective: Hypoxia-associated biomarkers profiling may provide information for prognosis, staging, and subsequent therapy. We aim to evaluate whether the quantitative gene and protein expression of hypoxic response tumor markers — carbonic anhydrase IX (CAIX) and hypoxia- inducible factor 1 alpha (HIF1A) — may have a role in predicting survival in advanced breast cancer of Indonesian population. Methods: Tumor tissues and peripheral blood samples were collected from treatment - naïve locally advanced (LABC) or metastatic breast cancer patients (MBC) at Wahidin Sudirohusodo General Hospital (Makassar, South Sulawesi) and its referral network hospitals from July 2017 to March 2019. The level of mRNA (of blood and tumor tissue samples) and soluble protein (of blood samples) of CAIX and HIF1A were measured by RT-qPCR and ELISA methods, respectively, besides the standard histopathological grading and molecular subtype assessment. The CAIX and HIF1A expression, patients’ age, tumor characteristics, surgery status, and neoadjuvant chemotherapy drug classes were further involved in survival analyses for overall survival (OS) and progression-free survival (PFS). Results: Forty (30 LABC, 10 MBC) eligible patients examined were 21 hormone-receptors positives (15 Luminal A, 6 Luminal B) and 19 hormone-receptors negatives (10 HER2-enriched, 9 triple-negative). The CAIX blood mRNA and CAIX soluble protein levels in hormone-receptors negative patients were higher than in hormone-receptor-positive patients (p < 0.05). In univariate analysis, both CAIX and HIF1A levels predict OS (except HIF1A protein) with CAIX tissue mRNA has the highest hazard ratio (HR 8.04, 95%CI:2.45-26.39), but not PFS. Cox proportional hazard model confirmed that CAIX tissue mRNA is the independent predictor of OS (HR 6.10, 95%CI: 1.16-32.13) along with surgical status and tumor advancement type (LABC or MBC). Conclusions: CAIX mRNA expression of tumor tissue in treatment-naïve advanced breast cancer has a predictive value for OS.

Background There is a role for the immune system in improving the outcome of peritonitis cases in children. Transfer factors are one immunomodulatory treatment that can increase the activity of natural killer (NK) cells to produce interferon-gamma (IFN-γ), which is thought to increase the phagocytic activity of macrophages. This study analyzed the effects of transfer factors on the phagocytic activity of macrophages in the intraperitoneal fluid of a Wistar rat model of peritonitis. Methods This experimental study had a post-test-only control group design and was carried out at the Laboratory of Pharmacology and Microbiology of Padjadjaran University, Bandung, Indonesia. It analyzed the effect of transfer factors on the phagocytic activity of macrophages in the intraperitoneal fluid of Wistar rats experiencing peritonitis after being injected with Escherichia coli. An unpaired comparative t-test was performed using the SPSS program to analyze the difference between transfer factor administration and macrophage phagocytic activity levels. Results There was a statistically significant difference between the phagocytosis index values of macrophages in samples treated with transfer factors and those that were untreated (p = 0.005). Conclusions Transfer factors increased the phagocytic activity of macrophages in a Wistar rat model of peritonitis. This suggests that transfer factors could have a role as an immunomodulatory treatment for peritonitis., Highlights • Transfer factors increase the activity of natural killer (NK) cells. • Transfer factors enhanced the phagocytic activity of macrophages in a rat model of peritonitis. • Transfer factors have a role as an immunomodulatory treatment in peritonitis cases.

Background Tuberculosis (TB) remains a major global health problem, in the top 10 causes of death. As a regulator of the immune response, T-helper (Th) cells activate other lymphocytes from the immune system, such as B cells, to destroy the TB pathogen by releasing CD4 and CD8 Th cells. Diabetes mellitus (DM) is a known cause of developing active pulmonary TB. Few studies have examined the biomolecular expression affecting Mycobacterium tuberculosis (MTB) and multidrug-resistant (MDR) MTB, which are associated with low immunity represented by TB in diabetes and CD4 and CD8 levels. Materials and methods This animal study used a post-test control group design. We performed an experimental study using 30 BALB/c mice, each weighing 25 g. It included six experimental animal groups, of which three had a diabetes condition induced using intraperitoneal streptozotocin, and all were infected with MTB or MDR TB. We evaluated the CD4 and CD8 levels in each group and analyzed the differences. Results We found a significant difference in CD4 and CD8 levels in MTB and MDR TB conditions. Conclusion This study shows that acute infection in experimental mice with MTB and MDR TB with or without diabetes had the highest levels of both CD4 and CD8 cells, which can be a sign of increased cellular immunity in a mice model., Highlights • Tuberculosis (TB) is still a major global health problem. • TB with comorbid diabetes mellitus (DM) are associated with increased CD4 and CD8. • CD4 and CD8 values are increased in animals with DM plus TB infection.

Traumatic brain injury (TBI) is a major cause of death and lifelong disability around the world that predominantly affects young and middle-aged people. Erythropoietin (EPO) is a promising therapeutic agent for a variety of neurological injuries including TBI due to its neuroprotective effects. Here we review the impact of exogenous erythropoietin administration on the expression of brain-derived neurotrophic factor (BDNF), stromal cell-derived factor-1 (SDF-1), and neuron-specific enolase (NSE) levels in cerebrospinal fluid after TBI as biomarkers for neuron regeneration and survival to predict TBI outcome., Highlights • Traumatic brain injury (TBI) is a major cause of death and lifelong disability. • Administration of erythropoietin (EPO) can benefit the clinical outcome of patients with TBI. • EPO treatment increases BDNF and SDF-1 expression in the brain. • BDNF and SDF-1 promote neuron survival and regeneration. • EPO is a promising therapeutic agent with neuroprotective effects.

Introduction: Post-concussion syndrome is common in young adults and can greatly interfere with the quality of daily life. It has a wide range of symptoms that require prompt and well-targeted treatment to avoid further brain impairment. Hyperbaric oxygen therapy (HBOT) is a promising regenerative treatment option for these patients to help prevent the progression of post-concussion syndrome. This study aims to determine whether HBOT accelerates the healing process and reduces symptoms in patients with post-concussion syndrome. Methods: 20 patients with post-concussion syndrome participated in this randomized controlled trial study. After receiving standard mild traumatic brain injury treatment in accordance with the Advanced Trauma Life Support guidelines, the patients were divided into HBOT and control groups. Matrix metallopeptidase 9 (MMP-9) levels and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) scores were used to compare the two groups (before HBOT & after 1st, 3rd, and 5th week). Results: The study sample was predominantly male (65%) with an average age of 60 years old. HBOT reduced serum MMP-9 levels by nearly 20 ng/mL (p < 0.001) compared with the control treatment. The efficacy of HBOT was also reflected in the RPQ scores, which were significantly lower in the HBOT group than the control group (before HBOT & after 1st, 3rd, 5th week) (-3.80 on RPQ-3, p = p Conclusion: HBOT ameliorated the symptoms associated with post-concussion syndrome through a mechanism that involves MMP-9 activity. The accelerated recovery observed in the present study supports the use of HBOT to treat post-concussion syndrome and potentially other forms of traumatic brain injury.

Background Head injury or traumatic brain injury is the leading cause of mortality and morbidity. Many modalities of neuroprotection had been developed in brain injury but there was no much information regarding folinic acid's effect on neuroinflammation associated with homocysteine, TNFα, IL-10, and HMGB1. Objective This study aimed to investigate whether folinic acid has improving effect on head injury model. Method This study was done in the rat's head injury model using modified Marmarou weight drop model. Fifteen rats were randomized and grouped into 3 groups: Group A: Folinic acid (+), head injury (−); Group B: Folinic acid (−), head injury (+); Group C: Folinic acid (+), head injury (+). Folinic acid was administered intraperitoneally with a dose of 60 mg/m2. Blood samples were taken immediately after head injury (H0), 12 h (H12), and 24 h (H24) after head injury from the lateral vein of tail. Serum level of homocysteine, TNFα, and IL-10 were measured using ELISA, and HMGB1 gene expression was measured with Real-Time RT-PCR. Results This study found serum level of homocysteine, TNFα, IL-10 and HMGB1 gene expression were markedly increased at all time points after head injury. Significantly lower level of serum homocysteine, TNFα, IL-10 and HMGB1 gene expression were found after 24 h treatment with folinic acid in group C compared to those in group B. Conclusion Folinic acid may have anti-inflammatory properties in traumatic brain injury by inhibition of serum level of homocysteine, TNFα, IL-10 and HMGB1 gene expression.

INTRODUCTION: Cerebral edema in traumatic brain injury (TBI) results from hyperpermeability of the bloodbrain barrier (BBB). One of the causes in BBB permeability disorders is the activation of matrix metalloproteinase 9 (MMP-9) which can be inhibited by the administration of doxycycline. Knowing the role of oral doxycycline administration as an inhibitor of MMP-9 activation on the level of MMP-9 in cerebral edema in traumatic brain injury. MATERIALS AND METHODS: This study was an experimental study in Wistar rats with a post-test control design consisting of one control group, one group with provoked brain injury, and one group with provoked brain injury followed by oral doxycycline administration. RESULT: There were significant differences in the level of MMP -9 between the control group, the provoked brain injury group and the provoked brain injury group followed by oral doxycycline administration with p-value = 0.01 (p

Introduction Neoadjuvant chemotherapy has become the standard form of treatment for locally advanced breast cancer. Chemoresistence is a problem that limits the effectiveness of chemotherapy. Therefore, predictive biomarkers are needed to choose the appropriate chemotherapy to the right patient. The role of NF-кb expression as a predictive biomarker of neoadjuvant chemotherapy response needs to be investigated in patients with locally advanced breast cancer who are treated with a regimen of cyclophosphamide-doxorubicin-5FU (CAF). Methods This observational study used the prospective cohort method to examine 62 samples. CAF was administered at 3-week intervals for 3 cycles of chemotherapy. The data utilized in this study include the positive and negative expression of NF-κB, ER, and HER2 overexpression. The cases were divided into groups that were responsive and non-responsive to the neoadjuvant chemotherapy. Results The average age in the youngest group was 26 years, and that in the oldest was 66 years. The highest age group was subjects in their 50s, which had 26 cases (41.9%). The majority of the cases were moderate grade with 38 cases (61.3%). The percentage of responsive subjects was higher in the groups with negative NF-κB expression (82.5%), positive HER2 status (85.7%), and negative ER status (71.9%). It was found that 37 cases (59.7%) were responsive to CAF, while 25 cases (40.3%) were non-responsive. There was a significant relationship between NF-κB expression and chemotherapy response (p, Highlights • Neoadjuvant chemotherapy is standard treatment for local advanced breast cancer. • Cyclophosphamide-doxorubicin-5FU (CAF) regimens are widely used in neoadjuvant chemotherapy. • NF-κB expression, ER status, HER2, and the CAF response are significantly related. • Cases with negative NF-κB expression were 10 times more likely to respond to CAF. • NF-κB expression should be considered as a predictive biomarker.

Tuberculosis infection causes a complex immunological response, where interactions between the pathogen and the host are unique, making it difficult to treat and control this disease. According to WHO, an estimated 1 million children became ill with TB, and 233,000 children died of TB in 2017. Bacillus Calmette-Guerin (BCG) vaccines continue to be the only vaccines to prevent Tuberculosis (TB). Studies suggesting the association of BCG scar with decreased childhood mortality in developing countries have rekindled the interest in BCG scar. However, the direct effect of the BCG scar remains unknown. We examined 76 cases in this study. All Subjects were diagnosed with Tuberculosis. BCG scars were examined directly when physical examination at the BCG vaccination site was performed. Tuberculin Skin Test was performed with 0.1 ml purified protein derivative (PPD) solution (5TU PPD/0.1 ml) injected intradermally. We examined the FOXP3 gene by real-time PCR and the level of Treg byELISA. The comparison of the mean Treg gene expression and the Treg protein content was higher in the positive scar group than in the negative scar group. It shows that Treg plays a role in the Tuberculosis during its active phase development. Treg protein levels were higher in the combination of positive TST and scar. It shows that BCG scarring is an essential marker of a well-functioning immune system. Cheap and straightforward initiatives like early BCG vaccinations, monitoring BCG scarring, and revaccinating scar-negative children could have an enormous immediate impact on global child survival.

BACKGROUND፡ Odontoid fracture frequently ensues after a cervical trauma, and most commonly at the junction between the dens and the body (type II odontoid fracture).CASE PRESENTATION: This report is focused on a 24-years-old male patient with right-sided hemiparesis, resulting from traumatic atlantoaxial dislocation with type II odontoid fracture. Cervical CT-scanning showed a spondylolisthesis of the C1-C2 complex with type II odontoid fracture, and the injury was treated using posterior reduction and internal stabilization. Therefore, hemiparesis was reduced, and during the follow-up period, our patients were disease-free.CONCLUSION: Early diagnosis and the appropriate management of atlantoaxial trauma is a possible approach towards preventing severe neurological deficits.

Background A head injury is a very dangerous condition that threatens human life. This study examines the use of caffeic acid phenethyl ester (CAPE) in reducing cerebral edema in cases of head injury. The purpose of this study is to demonstrate whether CAPE can improve various parameters related to the expression of Aquaporin-4 (AQP4) mRNA and the serum AQP4 levels in rat subjects. Methods This is a randomized controlled study using a posttest-only control group design that uses experimental animals—specifically, male Rattus norvegicus (Sprague Dawley strain) rats aged 10–12 weeks and weighing 200–300 g. This study used a head injury model according to Marmarou (1994) with minor modifications to the animal model fixation tool. The parameters of the AQP4 mRNA were examined with real-time PCR, while serum AQP4 levels were examined with sandwich ELISA. Results The AQP4 mRNA expression in rats that were given CAPE was lower than those not given CAPE, both on the fourth and seventh days; serum AQP4 levels in rats that were given CAPE were also lower than those not given CAPE, both on the fourth and seventh days. Conclusion Administration of CAPE in a rat model with head injury can reduce cerebral edema, mediated by AQP4., Highlights • Head injury is a major cause of mechanical brain cell injury and also catalyzes secondary damage. • Caffeic Acid Phenethyl Ester (CAPE) can reduce inflammatory processes, brain lipid peroxidation, and free radical damage. • CAPE treatment can cause a decrease in cerebral edema, mediated by Aquaporin-4 (AQP4).

Objectives : To investigate the correlation between Interleukin 17 (IL-17F) and the level of asthma control. Methods : This is a cross-sectional study of 40 subjects who were diagnosed with atopic asthma. All participants were recruited from the Allergy and Immunology Clinic, Prof. R.D. Kandou General Hospital, Manado, Indonesia, between April 2015 and April 2016. Total serum IL-17F measured by using Enzyme-Linked Immunosorbent Assay methods; and mRNA IL-17F was obtained by using real-time reverse transcriptase polymerase chain reaction. Level of asthma control was quantified by using asthma control test (ACT) scoring system. The correlation between IL-17F, mRNA, and level of asthma control was analyzed by using Pearson’s correlation coefficient (r). Results : There is a strong positive correlation between IL-17F serum level and Nathan’s ACT-score (r=0.969) which is statistically significant (p less than 0.001). Analysis of the correlation between mRNA IL-17F serum level and Nathan’s ACT-score revealed a strong positive correlation (r=0.963), which is statistically significant (p less than 0.001). Conclusion : These findings suggest that IL-17F plays an important role in asthma control. However, the role played by IL-17F in asthma pathogenesis are still questions to be answered. Saudi Med J 2018; Vol. 39 (7): 662-667 doi: 10.15537/smj.2018.7.22055 How to cite this article: Surachmanto EE, Hatta M, Islam AA, Wahid S. Association between asthma control and Interleukin-17F expression levels in adult patients with atopic asthma. Saudi Med J . 2018 Jul;39(7):662-667. doi: 10.15537/smj.2018.7.22055.

Introduction: Asthma is a chronic reversible inflammation which is caused by bronchial hypereactivity due to exposure to allergen and hyperproduction of certain specific IgE. Neutrophil in respiratory tract and high level of IgE in the blood serum is known to play in complex mechanism in asthma development. The role of total IgE serum and neutrophil serum in asthma development is still not well known. Aim: This study aim is to assess the correlation between level of total IgE and neutrophil serum with degree of asthma control. Methods: This is a cross sectional study with 35 adult subjects with atophy asthma (age 22-61), all of participant reside in Manado and its surrounding area. Degree of asthma control is categorized as intermittent, mild persistent, moderate persistent and severe persistent based on criteria by GINA. Patient with malignancy, sepsis, lung tuberculosis, diabetes mellitus, pregnant, and late stage chronic kidney disease are excluded from this study. Result: In this study there is no significant correlation between total IgE serum level and degree of asthma control (p>0.05.) also there is no significant correlation between each total IgE level and each degree of asthma control. There is significant positive correlation between neutrophil count and degree of asthma control (r = 0.309; pConclusion: The neutrophil count in serum is related to degree of asthma control. Especially neutrophil count in mild persistent is higher than intermittent asthma. There is no correlation between total IgE level with degree of asthma control in adult subject with atopic asthma.

Background: Severe musculoskeletal trauma can trigger an inflammatory response, and an excessive inflammatory response can lead to systemic inflammatory response syndrome and multiorgan failure. High-mobility group box 1 (HMGB1) is an early mediator pro-inflammatory cytokine in sterile injuries and a late cytokine mediator in infection and sepsis. Previous research has shown that administration of systemic lidocaine can inhibit HMGB1 expression in macrophages of septic rats. The aim of this study was to demonstrate the efficacy of systemic lidocaine to inhibit HMGB1 mRNA and protein in a BALB/c mouse model of sterile inflammation due to closed fracture musculoskeletal injury. Materials and Methods: Twenty adult male BALB/c mice were divided into lidocaine and control groups. The closed fracture musculoskeletal injury was performed by breaking the left thigh bone of the mice. Four hours after undergoing the closed fracture, the lidocaine group was treated with lidocaine intravenous (2 mg/kg). The same volume of distilled water was injected into the control group instead of lidocaine. HMGB1 mRNA expression was examined with real-time polymerase chain reaction, and HMGB1 protein level was determined with enzyme-linked immunosorbent assay. Results: The expression of HMGB1 mRNA and protein levels in mice that sustained inflammation due to a closed fracture musculoskeletal injury was significantly decreased in the lidocaine group (P < 0.00 and P < 0.00 for mRNA and protein, respectively). Conclusions: Intravenous administration of lidocaine effectively inhibited the inflammatory process in BALB/c mice that underwent closed fracture musculoskeletal injury by suppressing HMGB1 mRNA transcription and HMGB1 protein translation.

Background Traumatic brain injury (TBI) is a complicated condition that is the primary cause of death and disability in children and young adults in developed countries. Various kinds of therapy have been carried out in the management of brain injury, one of which is the administration of erythropoietin (EPO). There are not many studies in Indonesia have proven that EPO administration is effective on parameters such as stromal cell-derived factor 1 (SDF-1), brain-derived neurotrophic factor (BDNF mRNA), and neuron-specific enolase (NSE) in brain injury patients. The purpose of this study was to see how EPO affected BDNF mRNA expression, SDF-1 serum levels, and NSE levels in experimental rats with TBI. Methods This study was conducted using a rat head injury model. Fifteen rats were randomly assigned to one of three groups: A, B, or C. EPO was administered subcutis with a dose of 30.000 U/kg. Blood samples were taken after brain injury (H0), 12 h (H12), and 24 h (H24) after brain injury. Serum level of SDF-1 and NSE were measured using mRNA BDNF gene expression was measured with Real-Time-PCR, and ELISA. Results This study found EPO increase BDNF mRNA expression in group C at H-12 (7,92 ± 0.51 vs 6.45 ± 0.33) compared to group B, and at H-24 (9.20 ± 0.56 vs 7.22 ± 0.19); increase SDF-1 levels in group C at H-12 (7,56 ± 0,54) vs 4,62 ± 0,58) compared to group B, and at H-24 (11,32 ± 4,55 vs 2,55 ± 0,70); decrease serum NSE levels in group C at H-12 (17,25 ± 2,02 vs 29,65 ± 2,33) compare to group B and at H-24 (12,14 ± 2,61 vs 37,31 ± 2,76); the values are significantly different with p, Highlights • Traumatic brain injury (TBI) is a major cause of death and lifelong disability. • Erythropoietin (EPO) increasing mRNA BDNF expression and serum SDF-1 levels. • EPO decrease serum NSE levels. • Erythropoietin may have neuroprotective and anti-inflammatory properties.

Purpose: Host response to polytrauma occasionally has unpredictable outcomes. Immune response is a major factor influencing patient's outcome. This study evaluated the interaction of two main cytokines in immune response after major trauma, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10). Plasma level of these cytokines is determined by mRNA expression of these cytokines genes which may decide the outcome of polytrauma patients. Methods: This prospective multicenter trial held at four trauma centers enrolled 54 polytrauma patients [Injury Severity Score (ISS) ≥ 16]. Plasma levels and mRNA expression of IL-6 and IL-10 were measured for 5 days after trauma. Clinical evaluation was conducted to observe whether patients endured multiple organ dysfunction syndrome (MODS) and death. MODS evaluation was performed using sequential organ failure assessment (SOFA). Trauma load which in this study is represented with ISS, plasma level, expression of cytokine genes and patient's outcome were examined with correlation test and statistical analysis. Results: The elevated IL-6/IL-10 ratio indicated increased activity of systemic inflammation response, especially pro-inflammation response which bears higher probability of progressing to MODS and death. The decline of IL-6/IL-10 ratio with heavy trauma load (ISS > 30) showed that compensatory anti-inflammation response syndrome (CARS) state was more dominant than systemic inflammatory response syndrome (SIRS), indicating that malfunction and failure of immune system eventually lead to MODS and deaths. The statistical significance in plasma level of cytokines was found in the outcome group which was defined as bearing a low trauma load but mortality. Conclusion: The pattern of cytokine levels in inflammation response has great impact on the outcome of polytrauma patients. Further study at the genetic level is needed to investigate inflammation process which may influence patient's outcome. Key words: Polytrauma; Interleukine-6; Interleukine-10; mRNA expression; Multiple organ dysfunction syndrome

BACKGROUND: Transorbital penetrating intracranial injury (TOPI) is rare lesions, representing about 0.4% of traumatic brain injury. This uncommon injury has potentially severe and fatalities brain damage with high mortality rate if not promptly treated. CASE REPORT: We presented three patients with TOPI following penetration by a homemade metal arrow; unfortunately, two patients (cases 1 and 2) death on arrival at our hospital. As a survival patient (case 3), a 15-year-old boy presented with a homemade metal arrow entered through a right superior orbital fissure into the right cerebral hemisphere. Plain skull radiograph showed that the tip of the shaft was located in the right of the posterior cerebral hemisphere and confirmed by computerized tomography (CT) and three-dimensional CT of his brain. Injury to the right middle cerebral arteries was apparent on non-contrast CT angiography. Using a right occipital craniotomy approach with C-arm radiography fluoroscopy guidance, we successfully removed the arrow. Follow-up studies confirmed an excellent outcome. CONCLUSIONS: Pre-operative imaging is mandatory to evaluate the trajectory, brain, and vascular injury for appropriate surgical planning and post-operative care of patients with TOPI.

Objective: Evaluation of the neoadjuvant chemotherapy response can be performed by comparing the breast cancer burden and pathobiology before and after treatment. This study was aimed to investigate the pattern of dual-specific phosphatase 4 (DUSP4) mRNA expression in breast cancer cells before and after neoadjuvant chemotherapy. Methods: This was a longitudinal study. Twenty samples of matched breast cancer tissue taken from biopsy before and after chemotherapy were subjected to qRT-PCR to detect DUSP4 mRNA expression. Results: The mean value of DUSP4 mRNA expression in prechemotherapy breast cancer patients was 9.906±0.333 and that in breast cancer patients postchemotherapy was 10.016±1.062. In the responsive group, the rate of DUSP4 mRNA expression increased by 0.476 after chemotherapy. In the nonresponsive group, the proportion of DUSP4 mRNA expression likely decreased by 1.012. Statistical analysis found no significant correlation between DUSP4 mRNA expression prechemotherapy and the clinical chemotherapeutic response with p-value = 0.994 (p ≥0.05). A significant correlation was found between the postchemotherapy DUSP4 mRNA expression and the clinical chemotherapeutic response with p-value = 0.003 (p < 0.5). Conclusion: No significant difference was found in the mRNA expression of DUSP4 in pre- and post-neoadjuvant chemotherapy specimens. High DUSP4 expression postchemotherapy shows a substantial correlation with the chemotherapeutic response.

Background: A recent study has indicated the potential of metformin therapy for lupus in animal models, but there has been no study evaluating the effect on pristane-induced lupus. This study aims to evaluate the effect of intraperitoneal versus oral metformin on interferon (IFN)-γ levels and FOXP3 mRNA expression on pristane-induced female BALB/c mice. Methods: In total, 31 female BALB/c mice, aged 6 weeks, were intraperitoneally induced with 0.5 ml of pristane (2,6,10,14-tetramethylpentadecane). After 120 days, the mice were grouped and treated with various treatments: normal saline 100 mcl, oral metformin 100mg/kgBW, or intraperitoneal metformin 100mg/kgBW. After 60 days of treatment, all treatment groups were sacrificed, and kidney specimens prepared and stained using hematoxylin and esosin. Results: IFNγ levels of saline controls vs. oral metformin group was 309.39 vs. 292.83 pg/mL (mean difference 16.56 pg/mL; 95% CI 0.74-32.37; p=0.042), and saline control vs. intraperitoneal metformin group was 309.39 vs. 266.90 pg/mL (mean difference 42.49 pg/mL; 95% CI 29.24-55.73 pg/mL; p Conclusion: Metformin is a potential new therapy to reduce the levels of IFNγ and increase FOXP3 mRNA expression in mice models of systemic lupus erythematosus. Intraperitoneal metformin, i.e intravenous administration in human, could provide a novel route of administration to improve the effect of metformin for lupus patients.

Introduction High Grade Astrocytoma (HGAs) is a type of Glioma tumor, observed in less than 15% of all primary neoplasms in the central nervous system, and brain abscess is a relatively rare infection of the parenchyma area. This report is based on HGA cases resembling brain abcesses in girls with symptoms of progressive severe headache accompanied with hemiplegia. Case presentation An 11-year-old girl was admitted with symptoms of headaches experienced over a period of 4 months. The pain was more progressive, and the patient also has left hemiplegia. Furthermore, head CT scan results with contrast and brain MRI showed a brain abscess (space-occupying lesions – SOL), and tumor removal surgery was performed. The HGA results of Anatomy Pathology were obtained, and therapy was continued with the administration of the HIT-GBM-C protocol. Therefore, a follow-up was performed at 3, 6, 12, and 24 months, and no signs of recurrence were observed. Also, on the outcome of physical examination and brain MRI was within the normal limit. Conclusion This report shows a rare case of HGA evaluated to share similarities with the incidence of cerebral abscess in children. The tumor diagnosis is based on clinical, radiological and histological examination, principally handled through multi-modality therapy.

• Interaction of two main cytokines (IL-6 and IL-10) after major trauma comes from the mRNA expression of IL-6 and IL-10 gene.

A severe injury can trigger an inflammation response and excessive response can cause multiple organ failure. HMGB1 is an early inflammation mediator in sterile injury and a late inflammation mediator in infection. It is an important mediator in severe sepsis and always associated with the severity of organ failure. Previous studies showed that the administration of systemic lidocaine could inhibit the expression of HMGB1 on septic mice with musculoskeletal injury. Nine male adult Balb/c mice were grouped by simple random sampling method into three groups of intravenous lidocaine injection dosages: 2 mg/kg, 3 mg/kg, 4 mg/kg. Musculoskeletal injury was done by breaking the left femoral bone in a close manner. Peripheral blood sampling was done 4 hours after injury and 2 hours after lidocaine therap. To evaluate the expression level of HMGB1 mRNA, RT-PCR was used. The result of our study showed that intravenous lidoaine administration on the 3 groups could decrease the level of HMGB1. In conclusion, lidocaine hold an important role in clinical diseases by inhibiting HMGB1.

Background. Chemotherapy has become a standard of treatment in managing breast cancer. To achieve proper treatment for the right patients, the predictive marker is needed. Ki-67 is a biomarker of proliferation for solid tumor. Studies mentioned association of Ki-67 expression with chemotherapy response. The study aims are to evaluate whether Ki-67 expression detected by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) may predict clinical response to neoadjuvant chemotherapy in breast cancer.Methods. This study utilized a longitudinal study. IHC and qRT-PCR methods were used for detection of Ki-67 expression. Chemotherapy response was calculated using RECIST. Data were analyzed with Chi-square and Wilcoxon’s test.Results. There were 48 subjects in this study. Analysis of Ki-67 expression with chemotherapy response has a significant correlation withp=0.025(p=0.002(p=0.012(Conclusion. These results suggest that Ki-67 expression detected by both IHC and qRT-PCR is considered to be a predictor of clinical response to neoadjuvant chemotherapy in locally advanced breast cancer.

The aim of this study was to investigate the effect of mild hypothermia therapy (34–36°C) and the alterations of matrix metalloproteinase-9 (MMP-9) in 20 patients with high-risk traumatic brain injury (TBI). The neurologic status and outcome were assessed using Full Outline of UnResponsiveness (FOUR) score and Glasgow Coma Scale (GCS). A prospective randomized control study involved patients with high-risk TBI (FOUR score ≤ 7). Patients were randomized into two groups, with and without mild hypothermia therapy which were investigated within 24 and 72 h. The MMP-9 level, MMP-9 mRNA expression and -1562 C/T polymorphism were estimated using enzyme-linked immune sorbent assay (ELISA), reversing transcription polymerase chain reaction (RT-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Different levels of these variables were compared in the two groups. In the hypothermia group, the expression of MMP-9 mRNA and the level of serum MMP-9 were significantly decreased (P < 0.05) within 72 h. There was a highly significant correlation between the expression of MMP-9 mRNA and the level of MMP-9 protein (R2 = 0.741, r = 0.861, P < 0.05). The study did not find in -1562 C/T polymorphism. The patients’ outcome was improved significantly after mild hypothermia therapy (P < 0.05). The data obtained from this study show that mild hypothermia therapy down regulated the expression of MMP-9 mRNA, the MMP-9 protein level and increased the FOUR score and GCS in high-risk TBI patients within 72 h.

Background: Glioma is one of the most common primary brain tumours and conveys a dismal prognosis despite aggressive treatment. Several biomarkers have been studied in the hope of yielding better diagnostic accuracy and improving patient management. Besides survival, functional and neurological disability are concerns that have no lesser importance. In 2017, a disease-specific assessment tool – the Neurologic Assessment in Neuro-Oncology (NANO) scale – was developed to measure neurologic function in neuro-oncology cases. We sought to determine biomarkers that might be associated with neurological scale improvement in glioma patients. Methods: Glioma grade II-IV patients were recruited from three major hospitals in Jakarta-Tangerang. Isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter gene methylation were tested, as well as patients’ neurological function before surgery and three months after. Improvement in neurological scale (NANO scale) was considered positive if there was a decrement of ≥1 of the scale. Results: There were 54 patients included in the study. Mean age was 43.63 (14.723) years old, and 61.1% were male. As much as 16 (29.6%) carried a mutation in codon 132 of the IDH1 gene, and 33 (61.1%) were MGMT methylated. Median NANO scale score before and three months after surgery was 4 (0-12) and 3 (0-12), respectively. Neurological improvement was found in 44 (81.5%) of the patients. Among patients with MGMT promoter gene methylation, 90.9% showed neurological improvement (p=0.035; OR=5; 95%CI 1.122-22.272). Conclusions: Gliomas with MGMT promoter gene methylation are more likely to show neurological improvement three months after surgery.

BACKGROUND: Inflammation following aneurysmal subarachnoid hemorrhage (SAH) is associated with patient outcome. This study aimed to analyze the dynamics pattern of the pro-inflammatory interleukin (IL)-1β and anti-inflammatory cytokine IL-10 in the cerebrospinal fluid (CSF) following aneurysmal SAH.METHODS: This is a prospective observational study. The CSF was collected prior to surgery, and on the 2nd, 4th and 6th days after surgery. The CSF was then analyzed for IL-1β and -10 using enzyme-linked immunosorbent assay. Delayed Ischemic Neurological Deficits (DIND) was determined based on new neurological deficits within the first week after surgery. Data was analysed with T test or Wilcoxon Rank-Sum test to evaluate the pattern of biomarkers between DIND and non-DIND groups.RESULTS: There were 33 patients enrolled in this study, 16 patients (48.48%) who experienced DIND and 17 patients (51.52%) were non-DIND. There were significant increase dynamic levels of IL-10 and -1β in DIND patients (p

Background: Traumatic brain injury (TBI) has risen sharply, mainly due to increased use of motorized vehicles in countries with low and middle income. Traffic accidents are the main cause of TBI (60%) followed by falls (20%–25%) and violence (10%). Computed tomography (CT) is recommended for initial assessment in emergency services. Not only provides information and diagnosis to identify surgical needs, but also helps in evaluating patients and outcomes. Method: A retrospective study conducted using medical record data of neurosurgery patients who met the inclusion criteria in West Nusa Tenggara General Hospital in 2015 until 2017. The sample size is determined by consecutive sampling method. Result: Sample size was 209 patients. Male patients more common than female (78.95%). The highest age group at 21–30 years (21.53%) with average age was 31.66 years old. The initial median GCS was 10 points. The most common cause was motor vehicle accidents (MVA) with 176 cases (84.21%). The highest mortality rate was found in the severe brain injury group with 31 patients (14.83%). Average duration of treatment were 7.58 days. Conclusion: There was a significant relationship between age, initial GCS value, mortality rate, and length of stay for TBI patients with outcome predictions based on CT Marshall classification. Keywords: Traumatic brain injury, Outcome prediction factors of TBI, CT Marshall classification

Journal International Prihantono Abstract: Background: Proliferation is a distinct hallmarks of cancer. Ki-67 designated as a marker of proliferation in solid tumors. The proliferative activity of tumor demonstrated by expression of Ki-67 in breast cancer has been associated with a poor prognosis. Changes in the relative proportions of Ki-67 can be observed during chemotherapy and may correlated with clinical response in breast cancer. Purpose: Evaluate changes in mRNA expression of proliferation marker Ki-67 in breast cancer patients pre- and post-chemotherapy in relation with clinical response to chemotherapy. Method: This is a longitudinal study, 30 subjects breast cancer tissue samples pre- and post-chemotherapy using cyclophosphamide, adriamycin, 5FU regiment. We using qRT-PCR techniques to detect mRNA expression of Ki-67. Chemotherapy response is calculated using RECIST criteria. Results: Mean value of Ki-67 mRNA expression on breast cancer patients pre-chemotheraphy was 11.837??0.360. Mean value of Ki-67 mRNA expression on breast cancer patients post-chemotheraphy was 11.241??1.971. There was no significant correlation between expression of Ki-67 mRNA prechemotherapy with clinical response to chemotherapy, p = 0.862 (p ???0.05). There is a positive correlation between velocity of Ki-67 mRNA expression with clinical response with value of r = 0.378, this correlation was significant with p = 0.020 (p

Abstract Background: Asthma is a chronic inflammatory disorder of airway that involves many cells and elements. Chronic inflammation caused by increase Airway hyperresponsiveness that cause recurrent episodic symptoms of breathlessness, wheezing, chest tightness and coughing, especially at night or early morning. Interleukin 17F is a cytokine that plays an important role in the pathophysiology of asthma attacks. Some studies show a variety of IL-17F roles in the pathogenesis of airway inflammation due to an allergic reaction. Results: The study was conducted at the Prof. Dr. R. D. Kandou Manado Hospital, Indonesia. Samples were taken continuously until the number of meant samples was achieved. Blood samples were collected from 40 atopic asthmatic patients. From statistical analysis based on the hypothesis, there was positive correlation between mRNA levels of IL-17F and IL-17F in atopic asthmatic patient (p = 0.000 and r = 0.988). Conclusions: According these data suggest that levels of mRNA IL-17F and IL17F might be useful parameters for the diagnosis of atopic asthma patient

BACKGROUND: After stroke, there are dynamic changes of motor evoked potential (MEP), including latency, amplitude, central motoric conduction time (CMCT) and resting motor threshold (RMT) in cerebral. However, latency, CMCT, amplitude and RMT have not been clearly shown in acute ischemic stroke patients with motoric function impairment based on Modified Motoric Research Council Scale (MRCs). METHODS: Patients with motoric function impairment after acute ischemic stroke were recruited, scored based on MRCs and grouped. Latency, amplitude, CMCT and RMT (% intensity) was measured using transcranial magnetic stimulation (TMS). Latency, amplitude, CMCT and RMT of subjects based on affected hemisphere (AH) and unaffected hemisphere (UH); stroke onset; and motoric severity; were analyzed and compared statistically. RESULTS: Thirty-seven subjects with complete assessments were selected. Results of MEP size measurement between AH and UH showed that latency, amplitude, CMCT and RMT of AH and UH were significantly different (p

Context: Electrocardiographic (ECG) abnormalities are common following subarachnoid hemorrhage (SAH). It probably represents cardiovascular stress after SAH. Aims: The purpose of this study was to assess cortisol dynamics in relation to the ECG abnormality and disease course of SAH. Settings and Design: The study follows a consecutive cohort of aneurysmal SAH patients, who underwent surgery within 72 hours of onset, and they were followed up for 10 days. Materials and Methods: Serum cortisols, cortisol-binding globulin (CGB), adenocorticotropic hormone were measured (between 08.00-09.00 hours) preoperatively and then on postoperative days (PODs) 2, 4, 7, and 10. Electrocardiographs (ECG) were recorded on initial assessment and after surgery on daily basis in ICU. ECG abnormalities will be followed up by measurement of cardiac troponin T to quantify the myocyte necrosis. Statistical Analysis Used: Logistic regression analysis using commercial available software STATA 9. Results: A total of 44 patients (20 M and 24 F) were eligible for the cohort analysis. Average patient age is 52.02 years (52.02 ± 11.23), and 86% (6/44) arrived with World Federation of Neurosurgical Society Scale grade 3 or better. The ECG abnormality was found in 10 cases (22.7%), but the abnormal TnT (>1 μg/l) were found in eight cases, and two cases contribute to the mortality. The ECG abnormalities are significantly associated with total cortisol on day 4 (P < 0.05) and free cortisol on day 2 (P = 0.0065). Conclusions: Elevated levels of morning cortisol within the first four days after surgery are associated with the ECG abnormality.

Context: One of aneurysmal subarachnoid hemorrhage complication is delayed ischemic neurological deficits (DIND). It is postulated that cortisol dynamics might be associated with the severity of this complication. Aims: The goal of the study is to investigate whether the peak of morning serum cortisol levels are associated with the severity of its complication during the course of the disease. Settings and Design: This is a prospective cohort study conducted from January 2009 to June 2011, at our institution. Materials and Methods: The study follows a consecutive cohort of patients for 14 days after the aneurysmal subarachnoid hemorrhage. Serum cortisols, cortisol binding globulin, adenocorticotrophic hormone (ACTH) were measured pre operatively and then on post operative days (POD) 2, 4, 7, and 10. Blood was drawn to coincide with peak cortisol levels between 08.00-09.00 hours. Neurological examinations were conducted at least twice daily and patient outcome were graded according to modified Ranklin Scale. DIND was defined by a decrease in the Glasgow Coma Scale of two or more points compared to the status on POD 1. Statistical Analysis: All the results were analyzed using statistical software, Statistical Package for Social Sciences (SPSS v61; SPSS, Inc., Chicago, IL). Logistic regression analysis was used to compare the relationship between the variables. Results: Thirty six consecutive patients are collected, but only 28 patients (12 M and 16 F) were eligible for the cohort analysis. Average patient age is 50.75 years old (50.75±12.27), and more than 50% (15/28) arrived with World Federation of Neurologic Surgeons grade 3 or better. Elevated total cortisol levels of more than 24 mg/dl on day 2, 4, and 10 were associated with DIND, and the most significant being on day 4 (P=0.011). These patients also had a higher grade on the modified Ranklin scale of disability. Conclusions:This study shows that the elevated levels of morning total cortisol in the serum are associated with the onset of DIND during the disease course, and it's also associated with bad outcomes.