Chemical Composition and Neuroprotective Properties of Indonesian Stingless Bee (Geniotrigona thoracica) Propolis Extract in an In-Vivo Model of Intracerebral Hemorrhage (ICH).

Stroke is the world's second-leading cause of death. Current treatments for cerebral edema following intracerebral hemorrhage (ICH) mainly involve hyperosmolar fluids, but this approach is often inadequate. Propolis, known for its various beneficial properties, especially antioxidant and anti-inflammatory properties, could potentially act as an adjunctive therapy and help alleviate stroke-associated injuries. The chemical composition of Geniotrigona thoracica propolis extract was analyzed by GC-MS after derivatization for its total phenolic and total flavonoid content. The total phenolic content and total flavonoid content of the propolis extract were 1037.31 ± 24.10 µg GAE/mL and 374.02 ± 3.36 µg QE/mL, respectively. By GC-MS analysis, its major constituents were found to be triterpenoids (22.4% of TIC). Minor compounds, such as phenolic lipids (6.7% of TIC, GC-MS) and diterpenic acids (2.3% of TIC, GC-MS), were also found. Ninety-six Sprague Dawley rats were divided into six groups; namely, the control group, the ICH group, and four ICH groups that received the following therapies: mannitol, propolis extract (daily oral propolis administration after the ICH induction), propolis-M (propolis and mannitol), and propolis-B+A (daily oral propolis administration 7 days prior to and 72 h after the ICH induction). Neurocognitive functions of the rats were analyzed using the rotarod challenge and Morris water maze. In addition, the expression of NF-κB, SUR1-TRPM4, MMP-9, and Aquaporin-4 was analyzed using immunohistochemical methods. A TUNEL assay was used to assess the percentage of apoptotic cells. Mannitol significantly improved cognitive-motor functions in the ICH group, evidenced by improved rotarod and Morris water maze completion times, and lowered SUR-1 and Aquaporin-4 levels. It also significantly decreased cerebral edema by day 3. Similarly, propolis treatments (propolis-A and propolis-B+A) showed comparable improvements in these tests and reduced edema. Moreover, combining propolis with mannitol (propolis-M) further enhanced these effects, particularly in reducing edema and the Virchow-Robin space. These findings highlight the potential of propolis from the Indonesian stingless bee, Geniotrigona thoracica, from the Central Tapanuli region as a neuroprotective, adjunctive therapy.

Comprehension of Calcitriol Levels in Pregnant Women With Latent Tuberculosis and Immune Function in their Newborns.

Background: Pregnant women with latent tuberculosis infection (LTBI) may develop active tuberculosis infection and could infect their neonates, which could impair the child's immune system due to infection-mediated immunological responses. In order to develop a preventative TB program in this study, we desired to understand the impact of calcitriol in LTBI pregnant women and immunological responses in neonates. Patients and Methods: In three hospitals in Medan, North Sumatra, we implemented a case-control design with 84 pregnant women in their third trimester and their newborns. We determined the levels of calcitriol, cathelicidin, and interferon gamma (IFN-γ) in women between December 2021 and July 2022. These measurements were then compared to the newborns' levels of calcitriol, cathelicidin, IFN-γ, and Toll-Like Receptor (TLR) 2. Analyses were performed using the Chi-squared and Fisher's tests, while Spearman correlations were employed to assess for correlations. Results: 42 pregnant women with LTBI (interferon gamma release assay (IGRA) positive) and 42 pregnant women without LTBI (IGRA negative) participated in the study. The findings demonstrated that pregnant women with LTBI were at increased risk for calcitriol deficiency (Odds Ratio (OR) = 3.667, p = 0.006), which had an impact on the calcitriol levels of their unborn children (p = 0.038). TLR2 levels and calcitriol levels were substantially associated with LTBI pregnant women and their healthy neonates (p = 0.048; p = 0.005). Cathelicidin levels in the newborns of non-LTBI pregnant women were influenced by their higher calcitriol levels (p = 0.043). Pregnant women with LTBI had higher levels of cathelicidin and IFN-γ than those without it (p = 0.03; p = 0.001). Conclusion: Pregnant LTBI women's calcitriol levels had an impact on the calcitriol levels of their newborns. Mother's immunological responses and babies' calcitriol levels affected the levels of cathelicidin, IFN-γ, and TLR2 in newborns.

Effect of Phaleria Macrocarpa (Scheff.) Boerl Leaf Ethanol Extract on Serum IL-6 and TNF-α Levels in Diabetic Rats.

Background: Hyperglycemia conditions in diabetes mellitus (DM) can turn on pro-inflammatory cytokines like IL-6 and TNF-α. These cytokines play a role in insulin resistance and the development of DM complications. People in Indonesia have used Phaleria macrocarpa to treat diabetes, but the leaf of this plant has not been studied to see if it can reduce inflammation. Objective: This study aims to analyze the effect of ethanolic extract of Phaleria macrocarpa leaves (EEPML) in serum IL-6 and TNF-α levels of diabetic rats. Methods: This study was an experiment with a post-test-only control group design. Thirty 8-week-old male Wistar rats were used in the study. They were split into six groups: K1 was the normal control group; K2 was the DM control group; K3, K4, and K5 were given EEPML at doses of 125, 250, and 500 mg/KgBW; and K6 was given metformin 45 mg/KgBW orally once a day for 14 days. A high-fat diet and a 30 mg/KgBWi.p injection of streptozotocin were used to make the diabetic rat model. ELISA method for measuring serum IL-6 and TNF-α levels. The Kruskal-Wallis and the Mann-Whitney test were used to examine the differences between the groups. Results: There were significant differences between treatment groups in the mean levels of serum IL-6 (p=0.017), but there were no significant differences in the mean levels of serum TNF-α (p>0.05). Conclusion: Administration of Phaleria macrocarpa leaf ethanol extract 125 mg/KgBW reduced serum IL-6 levels but could not significantly reduce serum TNF-α levels in diabetic rats.

Study of the Molecular Dynamics Stability in the Inhibitory Interaction of Tenofovir Disoproxil Fumarate against CTLA-4 in Chronic Hepatitis B Patients.

Background: Tenofovir disoproxil fumarate (TDF) is a first-line nucleotide analog (NA) drug for hepatitis B therapy. Long-term NA therapy increases peripheral T cell levels to enhance antiviral response, while CTLA-4 inhibits the activation. Objective: This study analyzed the interaction between TDF and CTLA-4 through molecular docking. Methods: Target protein and ligand data mining were performed, and proteins were prepared by removing water molecules in the Discovery Studio 2019 software. The energy minimization was performed on ligands using Pyrx v.0.9.8 software. Protein-ligand docking was performed using Autodock Vina integrated with Pyrx v.09.8. Meanwhile, the docking of proteins was accomplished using the Haddock server. The BioVia Discovery Studio 2019 software visualized the interaction between the compound and the docked protein. Molecular dynamics simulations were carried out using the YASARA Dynamic program developed by Biosciences GmbH. Results: TDF ligand has good and stable inhibitory activity against the CTLA-4/B7-1 and CTLA4/B7-2 complexes. TDF docking has been shown to initiate conformational changes, indicating the ligand's inhibitory activity. The significant conformational changes based on superimposition results were shown by the CTLA-4/TDF/B7-2 and CTLA-4/B7-1/TDF complexes. TDF in all ligands undergoes bonding and displacement of binding sites. Conclusion: Treatment with TDF was predicted to have inhibitory activity against CTLA-4, especially in its complex form with B7-1 and B7-2.

The Role of Mesenchymal Stem Cell Secretome in the Inflammatory Mediators and the Survival Rate of Rat Model of Sepsis.

In sepsis, simultaneously elevated levels of pro-inflammatory cytokines and interleukin (IL)-10 indicate immune response dysregulation, increasing the mortality of the host. As mesenchymal stem cell (MSC) secretome is known to have immunomodulatory effects, we aim to assess the role of MSC secretome in the inflammatory mediators (NF-κB p65 and p50, TNF-α, IL-10) and the survival rate of a rat model of sepsis. In this study, forty-eight male Rattus norvegicus rats were divided into one sham group and three groups with sepsis induction: the control group and the sepsis-induced rat groups treated with 150 µL (T1) and 300 µL (T2) of secretome. The survival rate was observed per 6 h for 48 h and plotted using the Kaplan-Meier method. Compared to the control group, T2 showed a significant decrease in the relative expression of NF-κB and the serum TNF-α level, and a significant increase in the serum IL-10 level. Meanwhile, T1 showed a significant decrease in the serum TNF-α level compared to the control group. The Kaplan-Meier Log Rank test did not show significance in the distribution of survival between T1, T2, and the control group. However, from the 18th to the 36th hour, the survival rate of T2 was lower than the survival rate of the control group and T1, with a noticeable difference between T2 and the control group, as well as T1 at the 36th hour. At the 42nd hour, the survival rate of T2 was the same as the control group and remained lower than T1. In conclusion, MSC secretome regulated the inflammatory mediators in rat model of sepsis, with a dose of 150 µL being more effective.

Association Between Serum Cytotoxic T Lymphocyte Antigen (CTLA)-4 Level and Disease Progression in Patients With Chronic Hepatitis B.

Backgroud: Immune impairment, marked by increased expression of cytotoxic T lymphocyte antigen (CTLA)-4, promotes the disease progression of chronic hepatitis B. Objective: This study aimed to determine the association between serum CTLA-4 level and disease progression in patients with chronic hepatitis B. Methods: A cross-sectional study was conducted at Haji Adam Malik General Hospital Medan, Indonesia between October 2021 to September 2022. A total of 150 participants were enrolled. Patients aged 18 years or older with evidence of chronic hepatitis B, HBV-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC) were enrolled. Exclusion criteria were history of chronic hepatotoxic drug consumption, underlying liver abnormalities other than HBV infection, and liver injury due to metastasized malignancy from other sites. Serum CTLA-4 level was determined from serum using human CTLA-4 enzyme linked immunosorbent assay kit. Results: Most participants were males and aged between 40 and 60 years. Serum CTLA-4 level was positively associated with chronic hepatitis B progression (P<0.001). Serum CTLA-4 level was negatively correlated with serum platelet (P<0.001) and albumin levels (P<0.001) but positively correlated with serum ALT (P=0.045) and total bilirubin levels (P<0.001). Conclusions: Serum CTLA-4 level is associated with disease progression in patients with chronic hepatitis B.

Comparison of Gambier Extract (Uncaria Gambier Robx) and Angiotensin Receptor Blocker on Proteinuria Reduction and Antioxidants - Enhancement in Nephrotic Rat Models.

Background: Proteinuria is a significant clinical manifestation that causes edema in several diseases, including Nephrotic Syndrome (NS). Untreated proteinuria is strongly linked to the progression of kidney failure. One of the adjuvant therapies could be used to reduce proteinuria such as Angiotensin Receptor Blocker (ARB) including Losartan®. Gambier is a traditional medicinal plant widely known for its antioxidant effects. Catechin, a compound contained in Gambier Extract (GE), has been used to reduce microalbuminuria in diabetics. However, its application in NS has not been widely studied. Objective: This study compared the effects of GE and ARB in reducing proteinuria and increasing antioxidant activity levels, as well as reported histopathological findings in the nephrotic Wistar rat model. Methods: An experimental design study with a control group and a posttest was conducted. The experimental animals were divided into four groups: the control group (K1), the group with puromycin aminonucleoside (PAN) injection (K2), the group with PAN injection + GE (K3), and the group with PAN injection + Losartan® (K4). The standard GE used was Sarie Uncariae® by Toyo Brothers, PT while the ARB (Losartan®) was obtained from Novell, PT. Protein urine, the activity level of total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were assessed using the colorimetric method. Renal histopathology was assessed based on Rollerman's criteria. Results: Gambier extract significantly reduced proteinuria, as depicted by a decrease in protein/volume urine (p = 0.009), increased antioxidant activity, as illustrated by an elevation in T-SOD activity levels (p = 0.007), and tended to decrease MDA levels compared to Losartan®. Based on histopathological findings, GE tended to reduce the percentage of kidney damage in rats induced by puromycin. Conclusion: Gambier extract has been shown a higher antioxidant effect by increasing T-SOD activity levels, reducing proteinuria and also exhibiting a tendency to diminish kidney damage.

Factors affecting HBV DNA suppression in chronic hepatitis B patients treated with tenofovir disoproxil fumarate.

Background: This study aims to determine the factors affecting HBV DNA suppression in chronic hepatitis B patients with tenofovir disoproxil fumarate (TDF). Methods: A case-control was carried out from October 2021 to August 2022 on 182 chronic hepatitis B patients who had TDF therapy regularly for 24 weeks at H. Adam Malik and USU Hospitals in Medan, Indonesia. The history of the samples was obtained, followed by physical examination, and blood collection. CTLA-4 polymorphism examination was carried out using real-time PCR, while the serum CTLA-4 levels were assessed with ELISA. Results: The CTLA-4 -1661G>A polymorphism, genotype GG+AG, increased 1.52 times risk of not achieving HBV DNA suppression to TDF compared to genotype AA (p=0.041). High CTLA-4 levels increased 2.28 times risk, high HBV DNA levels increased 2.09 times risk, low ALT levels increased 1.95 times risk of not achieving HBV DNA suppression (p= 0.009, 0.026, 0.036, respectively). There was no relationship between gender, age, ethnicity, obesity, baseline AST, HBeAg, genotype, liver fibrosis and HBV DNA suppression after 24 weeks of treatment (p>0.05). Conclusions: The levels of CTLA-4, HBV DNA, ALT, and CTLA-4 -1661G>A polymorphism have a potential relationship with the suppression of HBV DNA in chronic hepatitis B patients with TDF.

The Comparison of Hospital Anxiety and Depression Scale-Anxiety Scores between Female Caregivers of People with Schizophrenia According to Gender Difference.

BACKGROUND: Caregiver plays an important role for a better outcome in people with schizophrenia, although it usually causes emotional distress for the caregiver. Anxiety is one of the emotional distress. Gender of schizophrenic patients is associated with the emotional distress of caregiver. The differences in HADS-A scores between female caregivers of people with schizophrenia according to gender in Indonesia remain unclear. AIM: To determine whether HADS-A scores are higher in a male group compare with the female group. METHODS: This study was an analytical study with a cross-sectional approach to determine the comparison of HADS-A score between 27 female caregivers of male schizophrenic patients (male group) and 27 female caregivers of female schizophrenic patients (female group) in Prof. Dr M. Ildrem Mental Hospital Medan, using a HADS rating scale. RESULTS: There is no difference between the male and female group in caregivers age, marital status, employment status, family income/month, education time, the relationship with people with schizophrenia, caring time, time spent / weeks, and the patients age, employment status, education time, PANSS score and number of relapses. The comparison between total HADS-A score between the male group and the female group is not significant with 9.52 ± 4.90 v 8.70 ± 4.49 (p = 0.53). CONCLUSION: HADS-A scores are not higher in caregivers of male with schizophrenia compared with caregivers of a female with schizophrenia.

Shared Psychotic Disorder (Folie À Deux): A Rare Case with Dissociative Trance Disorder That Can Be Induced.

BACKGROUND: Shared psychotic disorder was first introduced in the 19th century in France with the name Folie à deux. Since then, the concept of Folie à deux has been developed and produces several subtypes in France. In DSM, this disorder is called Shared Psychotic Disorder, and in ICD-10, it is called Induced Delusional Disorder. However, some of the classic subtypes of Folie à deux are not included in the above categories. CASE REPORT: We found a case of shared psychotic disorder between a 38-year-old male inducer, a Batak tribe with two female recipients, 34 and 36 years from the Batak tribe. They were found to share the same delusions and hallucinations, and inducers could make recipients into trance conditions. These three individuals did not get along with the surrounding community and often carried out activities and perform rituals together. CONCLUSION: Overall, our case has some unique features of folie à deux. In this case, there is a trance condition that can be induced that have not been reported in the literature or case reports related to Folie à deux.

Brain-Derived Neurotropic Factor Serum Level and Severity Symptom of Bataknese Male Patients with Schizophrenia in North Sumatera, Indonesia.

BACKGROUND: Schizophrenia is a severe mental disorder that is multi-causative and multi-factor, generally affecting about 1% of the population. The elevation level of brain-derived neurotrophic factor (BDNF) offers several protections from other neurodegenerative processes that occur in schizophrenia since this deficit of neurotrophic factors can contribute to changes in brain structure and function that underlie the schizophrenia psychopathology. AIM: To analyse the correlation between BDNF serum levels and symptom severity by using the Positive and Negative Syndrome Scale (PANSS) instrument in Bataknese male patients with schizophrenia. METHODS: This study was a correlative analytical study with a cross-sectional approach using the Positive and Negative Syndrome Scale (PANSS) instrument to assess symptom severity with 60 subjects of Bataknese male patients with chronic schizophrenia. Moreover, this research was conducted at the Psychiatric Hospital of Prof. Dr M. Ildrem Medan, Indonesia. BDNF serum was analysed with the Quantitative sandwich enzyme immunoassay technique by via Quantikine ELISA Human CXCL8/IL-8 HS. Also, the data analysis was performed through Spearman's correlative bivariate analytics using SPSS software. RESULTS: A negative correlation between the BDNF serum level and the negative scale PANSS score in men with schizophrenia (r = -0.820, p < 0.001) was found. Moreover, there is a negative correlation between BDNF serum levels and PANSS total scores in men with schizophrenia (r = -0.648, p < 0.001). CONCLUSION: BDNF serum level in Bataknese male patients with schizophrenia has a relationship that affects the severity of symptoms in schizophrenic patients, especially for negative symptoms.

Affective Psychopathology Towards the Quality of Life of Breast Cancer Patients with Radiotherapy in Medan, Indonesia.

BACKGROUND: Cancer has to become the scariest disease and tends to reduce the quality of life of the patient. Therefore, it is not only a medical treatment that needs to be conducted but also a psychological treatment. AIM: to analyse the relationship between affective psychopathology and the quality of life of breast cancer patients who are receiving radiotherapy treatment. METHODS: This research was a correlative analytical study with a cross-sectional approach using the Hospital Anxiety and Depression Scale (HADS) instrument to assess psychopathological features and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) to determine the quality of life. This research was conducted in March 2016-July 2016 at Vina Estetika Cancer Center Hospital, Medan, Indonesia. As many as 47 subjects were divided into two criteria; Inclusion criteria, participants with breast cancer who were undergoing radiotherapy, aged over 18 years, with HADS score ≥ 17, and the exclusion criteria, were patients suffering from chronic psychiatry diseases. RESULTS: Affective psychopathology was indicated to result in a significant negative correlation with the quality of life of breast cancer patients which whom were treated with radiotherapy with p = 0.035 and r = -0.267. This suggests that with a higher HADS, a decrease in quality of life will occur. CONCLUSIONS: Affective psychopathological comorbidities have a great influence on the quality of life of patients who are undergoing radiotherapy. Thus, cancer management must include screening for psychopathological morbidity. Moreover, psychological rehabilitation must also be provided along with the cancer treatment.

Indonesian Version of Addiction Rating Scale of Smartphone Usage Adapted from Smartphone Addiction Scale-Short Version (SAS-SV) In Junior High School.

BACKGROUND: The increase of smartphone user among Indonesian junior high school students, particularly for teenagers, indicates the addiction factor of the smartphone. AIM: This research is designed to adapt the Smartphone Addiction Scale-Short Version (SASS-SV) to Indonesian version based on cultural adaptation of the rating scale. METHODS: This study involves 300 participants consisted of 151 of male children and 149 female children with an average age is 13.27 years-of-old. The validity of concurrent was used to obtain the validity, while the internal consistency and Receiver Operating Characteristic (ROC) were conducted to confirm the reliability of the rating scale. RESULTS: In purpose to measure internal consistency, the Cronbach alpha has been applied. The Cronbach alpha value was 0.740, and Concurrent validity was checked to NMP the Nomophobia Questionnaire (NMP-Q) based on Indonesian version. The analysis of ROC showed that the value of Area under the Curve (AUC) was 0.997 (0.990-1.000), with cut-off value accounted for ≥ 32, a sensitivity value of 0.91 and specificity value was 0.973 for the male children. On the hand of female children, the results showed similarity with the AUC was 0.996 (0.998-1.000), and the cut-off, sensitivity and specificity values were accounted for ≥ 34, 0.91, and 0.974 respectively. CONCLUSION: The Indonesian version of SAS-SV provided acceptable validation results as well as the reliability, and this version can be used to evaluate the smartphone addiction in Indonesia.

The Comparison of Olanzapine and Risperidone Treatment in Male Schizophrenic Patients using Positive and Negative Syndromes Scale (PANSS).

INTRODUCTION: The most common method to compare olanzapine and risperidone is by calculating the score of positive and negative syndromes scale (PANSS). However, there were some conflicting results mentioned from previous studies. AIM: This study aimed to compare the treatment of olanzapine and risperidone using PANSS, limited to only male patients receiving inpatient treatment to obtain more significant results. METHODS: The subjects of this study were male schizophrenic patients in the acute phase of treatment (N = 68) who were hospitalised at the Mental Hospital Prof. Dr M. Ildrem, Indonesia. These participants were divided into two groups and treated with different atypical antipsychotics (olanzapine, 20 mg/day [n = 34]; risperidone, 6 mg/day [n = 34]). The scores of PANSS from both groups were collected from pre-test and post-test after 6 -week treatment. RESULTS: The improvement of the schizophrenia symptoms measured by PANSS after 6 weeks showed significant differences in the scores of PANSS between the male patient groups treated with olanzapine and risperidone (p-value < 0.001). CONCLUSION: The group of olanzapine shows a higher improvement of the scores of PANSS than that the group of risperidone.