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BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of death in Indonesia. The primary treatment of locally advanced BC is neoadjuvant chemotherapy (NAC). The rapid proliferation of tumor cells in a neoplastic microenvironment is largely due to hypoxia, which also encourages the development of chemoresistant BC. The master regulator of the hypoxia response is hypoxia-inducible factor-1α (HIF-1α). The response evaluation criteria in solid tumors (RECIST) is an objective response metric that demonstrates the efficacy of a NAC based mostly on the size of the tumor. Ca15-3 is the protein product of the MUC1 gene and is the most widely used serum marker in BC. The purpose of this study is to investigate the relationship between HIF-1α and RECIST and between Ca15-3 and RECIST and to assess the relationship among all of them in BC. METHODS: This observational study used the prospective cohort method included 11 patients with histopathologically confirmed BC, specifically invasive ductal carcinoma. We evaluated the changes in HIF-1α and Ca15-3 serum levels using ELISA and measured tumor lesions with RECIST. The procedure was carried out twice. Serum levels were measured at baseline, and after receiving two cycles of NAC (5 weeks). RESULTS: Among the 11 patients included in this study, HIF-1α, Ca15-3, and RECIST decreased significantly after NAC. The changes in RECIST correlated with Ca15-3: each unit decrease in RECIST score was associated with a 0.3-unit decrease in Ca15-3 levels (p = 0.019). CONCLUSIONS: There was a decrease in HIF-1α, followed by a decrease in Ca15-3 and RECIST in response to chemotherapy. There was a statistically significant correlation between Ca15-3 and response to chemotherapy. This study evidences the relationship between factors that shape the local tumor microenvironment.

Introduction: A major public health problem, brain injury can cause disability and death. Managing traumatic brain injury (TBI) can involve surgical interventions (e.g., evacuation and decompressive craniotomy) and/or conservative interventions without surgery (e.g., oxygenation, resuscitation, antibiotics, osmotherapy, and analgesics). Lactate, a biomarker that exerts physiological effects, is sensitive to the lack of oxygen and ischemia in organs such as the brain in both types of interventions. The aim of our study was thus to compare lactate concentrations in patients with closed brain injuries after conservative and surgical interventions. Methods: In a cohort study, lactate concentration between patients with TBI in the conservative versus surgical intervention groups were analyzed using the chi-square test, the independent t test, and Spearman’s correlation test. Results: Lactate concentrations in patients with closed brain injuries at the baseline, 24-hour, and 72-hour blood sampling time points did not significantly differ between conservative and surgical interventions (ρ > 0.05). However, reductions in lactate concentrations after 24 and 72 hours did significantly differ between the intervention groups, despite being more reduced in surgical interventions (ρ = 0.001) than in conservative ones (ρ = 0.002). Lactate concentrations were also significantly lower after 24 and 72 hours in the surgical intervention group for patients with epidural hematoma (EDH, p= 0.001) than ones without EDH (ρ < 0.001). Conclusion: Lactate concentration is a reliable prognostic predictor for assessing the severity of brain injury other than the GCS, another common clinical predictor.

Introduction The matrix metalloproteinase-9 (MMP-9) inhibition is an important target in the treatment of traumatic brain injury. Recent studies have shown that Minocycline may have MMP-9 inhibition activity. This study aims to determine the effect of minocycline in inhibiting MMP-9 in cases of head injury which has not been studied much. Methods This research was conducted using a laboratory experimental method on rats with a post-test control group design. The research was conducted at the Animal Laboratory, Faculty of Medicine, Hasanuddin University for a period of 2 weeks. The research population was rats with traumatic brain injury and rats without traumatic brain injury as controls. The sample size for each group was determined with Federer's formula, the minimum number of samples for each group was 9 experimental animals (a total of 27 mice in this study). Group 1 are control group, group 2(TBI) are rats with a traumatic brain injury, and group 3 are rats with a traumatic brain injury who was given minocycline. Results The mean value of MMP-9 in group 2 (TBI) was 0.610116 ng/ml compared to the control mean value of 0.519300 ng/ml. The mean value of MMP-9 in group 3 (TBI+M) was 0.552674 ng/ml. From the ANOVA test, there was a significant relationship with a p-value = 0.001 There was a statistically significant relationship between the administration of minocycline and the decrease in MMP-9 levels in traumatic brain injury in Wistar rats. Conclusion The level of MMP-9 in Wistar rats with traumatic brain injury who were given minocycline was shown to be significantly lower than that of those without minocycline treatment. This result showed that minocycline has the potential to inhibit the increase of MMP-9 levels in traumatic brain injury.

Background: Researches towards Glioblastoma multiforme therapy (GBM) has been performed, especially in finding the tumor’s genetic cellular expression. The overexpression of EGFR, frequently found in human malignancies, is known to significantly impact cancer cells hallmark traits, such as increased cell survival, proliferation and invasion. This research is performed to figure out the synergistic effect of temozolomide, the main chemotherapy regimen used, and the monoclonal antibody anti-EGFR nimotuzumab in inhibiting the growth of GBM cells in vitro.Methods: We performed cell cultures using GBM U87MG cells and administered nimotuzumab 1000µg/ml and temozolomide 20 µg/ml in different sequences and timings. Inhibition of GBM cell growth is evaluated by measuring Ki-67 and ?H2AX levels using flowcytometry and tested with one-way ANOVA. Data were analyzed using SPSS version 21 for Windows.Results: Levels of Ki-67 were in the control group (23.17±1.72), nimotuzumab monotherapy (15.43±1.70), temozolomide monotherapy (14.80±1.37), simultaneous therapy (10.73±1.19), nimotuzumab 24 hours before temozolomide (10.57±1.05), and nimotuzumab 48 hours before temozolomide (14.47±1.37). The level of ?H2AX is measured in the control group (11.90±1.25), nimotuzumab monotherapy (29.33±1.91), temozolomide monotherapy (28.13±1.58), simultaneous therapy (41.53±3.51), nimotuzumab 24 hours before temozolomide (39.56±2.06), and nimotuzumab 48 hours before temozolomide (35.93±3.56).Conclusion: This research shows that administration of nimotuzumab simultaneously with temozolomide and nimotuzumab 24 hours before temozolomide effectively inhibits the growth of U87MG GBM cells. Inhibition of EGFR expression before temozolomide administration is able to increase DNA damage and inhibit the proliferation of glioma cells.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide that imposes a significant burden on both individuals and their families. Many of the symptoms experienced by patients with TBI are thought to be mediated by the neuroinflammatory process that occurs after the primary injury. Therefore, the present study aimed to determine the effect of diphenhydramine HCl (DPM) on serum levels of the inflammatory cytokine tumor necrosis factor-α (TNF-α) after TBI.This was an experimental study with a pre- and post-test control group design. A total of 10 adult Wistar rats were divided into 2 groups, the DPM group and the placebo group. The effect of DPM on serum levels of TNF-α was evaluated at 30 min, 2 h, and 24 h after the induction of experimental TBI in the rats using Marmarou's weight-drop model.TNF-α levels in the DPM group significantly decreased from 0 min to 24 h after TBI (p = 0.004). In the placebo group, TNF-α levels significantly increased from 0 min to 24 h after TBI (p 0.001). Post hoc analysis found that TNF-α levels in the DPM group decreased significantly from 30 min to 2 h and from 2 h to 24 h after TBI (p = 0.019 and p = 0.005, respectively).The results of this study suggest that administration of DPM causes a reduction in serum levels of TNF-α, indicating that DPM has a significant anti-inflammatory effect in experimental rats after TBI.

Neuropathic pain is a major problem whose pathogenesis is not known yet, which makes it difficult to treat. Effective treatment of neuropathic pain usually uses multimodal therapy that takes a long time but causes major health problems, which are commonly found in women over 50 years of age and are generally caused by lumbar radiculopathy due to lumbar spinal stenosis. The narrowing of the spinal canal resembles an ischemic condition that can increase the expression of VEGF in the dorsal root ganglion and then result in shortened walking distance (intermittent claudication). The effect of VEGF is thought to be through binding to VEGFR1 and VEGFR2, whose levels are increased in conditions of hyperalgesia and neuropathic pain. Immune mechanisms play a role in the pathogenesis of neuropathic pain, through the balanced process of pro-inflammatory cytokines and anti-inflammatory cytokines, TGF-β, which are immunosuppressive. MLC901 is a simplified traditional medicine formula from MLC601, which affects the nervous system through three main mechanisms, namely neuroprotection, neuro-regeneration and neuro-restoration. Elevated levels of MLC901 promote angiogenesis. This review discusses the effect of MLC901 on miR30c-5p expression, TGF-β expression, VEGF receptor expression, degree of axon demyelination and changes in neuropathic pain behaviour in experimental animals experiencing neuropathic pain using the circumferential spinal stenosis method. These findings may provide new targets for further scientific research on the molecular mechanisms of neuropathic pain and potential therapeutic interventions.

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 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 The combination of stromal vascular fraction (SVF) and platelet-rich plasma (PRP) is effective at increasing the concentration of growth factors including transforming growth factor-β (TGF-β). The increase in this growth factor is expected to accelerate the healing of burns. This study aims to determine the effect of giving a combination of SVFs and PRP on TGF-β levels in the healing process of deep dermal burns. Methods This was an experimental study in 64 rats using a post-test control group design consisting of 1 group of SVFs and PRP combination injection treatment group, 1 group given a topical combination of SVFs and PRP, 1 group given Vaseline, and 1 control group. Results There was a significant difference in TGF-β levels between the deep dermal burns group that was given a combination of SVFs and PRP injection and topical, the Vaseline group, and the control group with p-value, Highlights • The combination of SVFs and PRP is effective at increasing the concentration of growth factors. • Administration of SVFs and PRP by injection was not better than topical at increasing the expression of TGF-β. • The combination of SVFs and PRP increased the level of TGF-β in the healing process rats model.

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.

Trauma to the extremities is a common major health problem that requires special attention because it can have a dangerous impact on both the viability of the limb and the patient's life. Hyperbaric oxygen therapy is an alternative therapy hypothesized to improve the prognosis in lower extremity trauma.We present a series of 7 cases of lower extremity trauma treated with hyperbaric oxygen therapy: soft tissue loss, neglected chronic burn injury, high-voltage electrical burn, gas gangrene, crush injury, chemical burn, and excoriation with skin loss.Hyperbaric oxygen therapy involves giving 100% oxygen in a chamber at pressures above atmospheric pressure (2-3 atm absolute [ATA]). It can increase oxygen delivery to peripheral tissues with vascular compromise, cytogenic and vasogenic edema, and cellular hypoxia caused by limb trauma.Hyperbaric oxygen therapy has many benefits in lower extremity trauma for wound recovery, preventing complications, and helping patients return to daily activities.

Neuropathic pain is a major problem to date because of its high prevalence and lack of effective treatment. Neuropathic pain processes can be influenced by many factors and at various levels of the nervous system, including progesterone and the opioid system. The various mechanisms of the effect of progesterone on pain are still controversial, while the effect of progesterone on the activation of the opioid system also needs to be proven. This study aimed to determine the effect of progesterone on pain through the modulation mechanism of the opioid system.This research is a completely randomized experimental study using male wistar rats aged around three months at the Experimental Animal Laboratory, Department of Medical Biochemistry, Faculty of Medicine, Airlangga University.The result was analyzed by using statistical analysis of two independent samples (It was shown that there was a significant difference in the delta (δ) opioid receptor expression between the control group and the progesterone group, which indicated that progesterone causes an increase in the delta (δ) opioid receptor expression in the spinal cord.

How far the role of innate immunity and adaptive immunity do in children who have been BCG vaccinated in controlling the course and the severity of the TB disease has not been completely known. Mycobacterium tuberculosis entry to the body will be recognized by Toll-like receptors found on macrophages, neutrophils, and dendritic cells as part of the innate immune response, after which the dendritic cells will then present the antigen to lymphocyte T0 cells and initiate the adaptive immune response (of which CD4 T cells have an important role in). Was one or were both of these immune responses function well or not in a BCG Vaccinated Children with TB?This study aim to find a better understanding of the role of innate immune response assessed by TLR2/TLR4 mRNA gene expression and serum TLR2/TLR4 levels, while the role of adaptive immune response is assessed by analyzing serum CD4 level in children with TB who have had BCG vaccination.This cross-sectional study was conducted among children with TB at the outpatient and inpatient wards at Bhakti Medicare and Jakarta Islamic Hospital. Expression of mRNA gene was measured using the Boom method and protein serum levels were measured using the ELISA method. The results were analyzed by using the SPSS v.23 program.Sixty-nine children were recruited as subjects. In this study, 68.1% of whom had BCG scars. TLR4 mRNA gene expression was found to be higher than TLR2 mRNA gene expression. Serum CD4 level was found to be highest out of TLR2 and TLR4 level, but serum TLR2 level was higher than TLR4 level. TLR2/TLR4 mRNA gene expression, serum TLR2/TLR4 levels, and CD4 levels in subjects with BCG scar were also found to be significantly higher than in subjects without BCG scar (p 0.001). There was a significant positive correlation between TLR2/TLR4 mRNA gene expression and serum TLR2/TLR4 levels (r = 0.860; r = 0.864; p 0.001) and between serum levels TLR2/TLR4 with serum CD4 levels (r = 0.822; r = 0.832 p 0.001).As early as possible, BCG vaccine administration is needed in endemic countries, but it must be ensured that scars can be formed. It is also important to control Latent TB Infection (LTBI) to prevent transmission and relapse of disease.

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.

Damaged neural tissue caused by SCI could induce vascular endothelial growth factor (VEGF) that can worsen the condition in the late phase by increasing vascular permeability, thus inducing tissue oedema, which can worsen the infarction. MLC 901 has been widely used in Asia for stroke patients because its mechanism is known to down-regulate VEGF levels in ischemic tissue.Ten Sprague-Dawley rats were used in this experiment. To create a severe spinal cord injury in animal models. The animals were then randomly divided into two groups. MLC 901 was given to the first group, which was the intervention group, and placebo to the second group, which was the control group.This study showed a decrease in the mean VEGF mRNA expression in the group given MLC 901 compared to the control group, which had a very high mean VEGF mRNA expression starting after 1 h of administration of MLC 901 until day 14 after spinal cord injury. In addition, there was a decrease in VEGF levels in the MLC 901 group compared to the control group from 3 h after spinal cord injury (1 h after MLC 901 administration) to 14 days after spinal cord injury.It can be concluded that administration of MLC 901 can reduce vascular permeability, one of the mechanisms that is thought to occur is to reduce VEGF levels. MLC 901 also maintains the neuroprotective effect provided by VEGF by maintaining this level above the basal level until day 14.

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.

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.

Background The healing process of burns includes coagulation, inflammation, and remodeling. Vascular endothelial growth factor (VEGF) is involved throughout this healing process. Stem cells from the platelet-rich plasma (PRP) with stromal vascular fraction (SVF) can increase concentrations of growth factors, including VEGF. This is expected to accelerate burn healing. The aim of this study was to determine the effect of a combination of PRP and SVF on VEGF levels in a rats model of deep dermal burn wound healing. Materials and methods This is an experimental research study in rats using a post-test control group design with 4 groups: A) control, B) Vaseline, C) topical PRP and SVF, and D) PRP and SVF injection. Burn wounds were induced according to the modified Guo method. Results In a rats model of deep dermal wound healing, topical Vaseline significantly increased serum VEGF compared to control. Topical application and injection of stem cells also significantly increased serum VEGF compared to control and Vaseline. The VEGF concentration was significantly higher following injection of PRP and SVF, suggesting that the injection route is more effective at increasing VEGF levels compared to the topical application of stem cells. Conclusion The combination of PRP and SVF, either by injection or topical application, can increase VEGF levels during the healing process from deep dermal burns., Highlights • Stem cells can increase concentrations of growth factors. • Topical application and injection of stem cells significantly increased serum VEGF compared to control. • The VEGF concentration was significantly higher following injection of PRP and SVFs. • The injection route of stem cells is more effective at increasing VEGF levels compared to the topical application.

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.

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 Human mobility group box 1 (HMGB1) is a novel biomolecular agent which has a major part in inflammation process. HMGB1 has been known to be a strong pro-inflammatory factor as damage associated molecular pattern (DAMP) which its interaction with its receptor, the receptor of advanced glycation end products (RAGE), will cause positive amplification of inflammation signalling pathway. Brain injury is one of the major contributors for disability and death which neuroinflammation has a major role in its pathogenesis and influencing its outcome. In neuroinflammation, it has been described that HMGB1 may have a pivotal role in the process. Objective The objective of this article is to review the role HMGB1 in brain injury and its immunomodulatory properties. Methods A comprehensive search of literature was conducted in PubMed (NIH), Scopus, EMBASE, and Google Scholar database using keyword combinations of the medical subject headings (MeSH) of “HMGB1” and “Brain Injury” and relevant reference lists were also manually searched. All relevant articles of any study design published from year 1990 till June 2020, were included and narratively discussed in this review. Results Twenty-four articles were shortlisted and reviewed in this article. Through these articles, we synthesis information on the function and metabolism of HMGB1, immunomodulatory effect of HMGB1, clinical findings and other potential treatment involving HMGB1, and role of HMGB1 protein in brain injury. Conclusion HMGB1 has a strong pro-inflammation property which predominantly acts through RAGE pathways.Review registration number reviewregistry966 in www.researchregistry.com., Highlights • HMGB1 has a strong pro-inflammation property which predominantly acts through RAGE pathways. • This pro-inflammatory process needs to be balanced with anti-inflammatory agents for homeostasis. • Further studies are needed to support anti HMGB1 therapy in inflammation process.

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.

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.

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.

Objective Traumatic brain injuries have high mortality rates in many countries. Chemical parameters such as blood osmolarity, serum blood sugar, and coagulation factors can be used to assess the prognosis of a brain injury. Increased intracranial pressure and swelling of the brain are clinical manifestations of brain injury. One option for non-operative treatment is the use of mannitol (MT). This research aims to determine the dosage of MT 20% that demonstrates better levels of safety and effectiveness, based on the evaluation of 3 laboratory-test parameters. Method This research is a prospective cohort with a total sample of 30 patients with moderate brain injuries, who are divided randomly into two groups of different dosages of MT. Results The results are analyzed using repeated measures ANOVA tests and are significant if p 0.05). Conclusion MT 20% does not affect blood osmolarity, serum blood sugar, and coagulation factors.

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.

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: Valeriana officinalis has often been used to treat sleep disorders as a traditional medicine for 2000 years. The sedative effect of valerian extract is facilitated by the GABAA receptor β3 subunit. The aim of this study is to determine the effect of valerian extract on GABRB3 gene mRNA expression and sedative effect in BALB/c mice. Methods: This is an experimental preclinical study using a posttest-only control group design. A total of 20 BALB/c mice were randomly allocated into four groups consisting of five mice each. Group I was given 5 ml of Aqua Dest (distilled water), group II was given 0.025 mg/10 g of diazepam, group III was given 2.5 mg/10 g of valerian extract, and group IV was given 5 mg/10 g of valerian extract. The drugs were administrated for seven days through a gastric gavage. The rotarod test was performed on the seventh day. A blood sample was taken on the first day before drug administration and after the rotarod test on the seventh day to be analyzed using quantitative real-time PCR. Results: GABRB3 gene mRNA expression showed a significant increase in groups II, III, and IV (p Conclusions: GABRB3 gene mRNA expression was significantly increased after the administration of valerian extract. Based on the rotarod test, valerian extract and diazepam had a clinically similar sedation effect. A higher dose of valerian extract does not yield a higher level of GABRB3 gene mRNA expression nor sedative effects.

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

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.

Background: During the last two decades, research about GATA-3, Ki-67, p53 expressions have been done, but it is still a debate on their use in predicting breast cancer patients’ prognosis and survival rate. Expressions of GATA-3 decreased with increasing of histopathology grading of breast cancer and increase with decrease of histopathology grading of breast cancer. The level expression of Ki-67 has a positive relation with breast cancer histopathology grading. p53 has no correlation with high grade differentiation of breast cancer. p53 is a transcription factor which is activated as a part of cellular stress response that can regulate genes’ cellular process, including apoptosis and senescence. Aim: To determine correlation between expressions of GATA 3, Ki-67 and p53 with histopathology grading of breast cancer in Makassar, Indonesia. Methods: Antibody monoclonal GATA 3, Ki-67 and p53 on the nucleus cell were detected with immunohistochemistry method. The positive and negative expressions of GATA 3, Ki-67 and p53 were assessed using scoring system according to the proportion of positive cell and coloring intensities. Results: There is no correlation between the higher positive expression ofp53 and higher expression of histopathology grading of breast cancer (P = 0.089). While Ki-67 had positive association with higher grade malignancy (P = 0.03). However, there was no association between GATA-3 expression and histopathology grading. Conclusion: In our research we found there is no correlation between higher expression of p53 and low expression of GATA-3 with higher histopathology grading of breast cancer. High expression of Ki-67 have significantly statistic analysis with high expression of histopathology grading of mammary cancer.

Background: Cortisol dynamics in serum might be related to clinical vasospasm, also known as delayed ischemic neurological deficits (DIND). Two vasoactive substances that play a role in pathophysiology of DIND are endothelin-1 (ET1) and nitric oxide (NO), both are proved associated with cortisol. This study aimed to know how cortisol play a role on ET1/NO ratio and its relationship to DIND.Methods: This was a prospective cohort study for the first 14 days after aneurysmal subarachnoid hemorrhage (SAH). Patients with inclusion criteria will be enrolled for blood test before surgery, and post-operative day 2, 4, 7, and 10 (between 8:00-9:00 AM). The blood tests were performed for cortisol, ACTH, CBG, NO, and ET1. Free cortisol is calculated with Coolens equation. Logistic regression was used to see the interaction model and its scale. Bivariate analysis (corelation) was used to see the relationship between total cortisol, free cortisol, NO, ET1, and clinical vasospasm (DIND).Results: Forty-four patients are enrolled into this study (20 male; 24 females). Mean age is 52.02 years (52.02 ± 11.23). There were 29 patients (66%) within DIND group and 15 patients Non-DIND as the control group. The mean of cortisol level shown is significantly higher in DIND group (35.99 ± 14.24) µg/dL compared to Non-DIND group (19.57 ± 6.19) µg/dL, p < 0.001. The mean of free cortisol level was significantly higher in DIND group (2.06 ± 1.094) µg/dL compared to non-DIND group (0.838 ± 0.365 µg/dL; p < 0.001). The Scatter Plot graph show that correlation of cortisol with ET1/NO ratio started increasing on day 4 and became stronger on day 10.Conclusion: Cortisol is associated with DIND following aneurysmal SAH, probably through its role in keeping the balance between ET1 and NO level. (Med J Indones. 2013;22:161-6. doi: 10.13181/mji.v22i3.585) Keywords: Cortisol dynamics, delayed ischemic neurological deficits, endothelin-1, nitric oxide