Associations between pesticide exposure with biomarkers of stroke risk factors in farmers.

The extensive use of pesticides may cause acute and chronic intoxication. Therefore, this study aimed to reveal the associations between pesticide exposure and serum markers for stroke risk factors in farmers. A cross-sectional study was conducted with farmers, who used chemical pesticides in Seloprojo Village, Ngablak District, Magelang Regency, Central Java Province, Indonesia. A questionnaire containing demographics, pesticide use, and aspects related to work was employed. Measurements of serum cholesterol, uric acid, glucose, cholinesterase, and fibrinogen levels were also conducted. Of the 106 subjects, 31 (29.2%) used organophosphates as chemical pesticides. There was a significant difference between organophosphate and nonorganophosphate groups in plasma fibrinogen levels. The organophosphate group had higher levels of fibrinogen (292.29 ± 67.56 mg/dL) than the non-organophosphate group (255.24 ± 38.90 mg/dL). Of the studied risk factors for stroke, there is a significant association between organophosphate exposure and increased plasma fibrinogen levels.

Beyond invasive biopsies: using VASARI MRI features to predict grade and molecular parameters in gliomas.

BACKGROUND: Gliomas present a significant economic burden and patient management challenge. The 2021 WHO classification incorporates molecular parameters, which guide treatment decisions. However, acquiring these molecular data involves invasive biopsies, prompting a need for non-invasive diagnostic methods. This study aims to assess the potential of Visually AcceSAble Rembrandt Images (VASARI) MRI features to predict glioma characteristics such as grade, IDH mutation, and MGMT methylation status. METHODS: This study enrolled 107 glioma patients treated between 2017 and 2022, meeting specific criteria including the absence of prior chemotherapy/radiation therapy, and the presence of molecular and MRI data. Images were assessed using the 27 VASARI MRI features by two blinded radiologists. Pathological and molecular assessments were conducted according to WHO 2021 CNS Tumor classification. Cross-validation Least Absolute Shrinkage and Selection Operator (CV-LASSO) logistic regression was applied for statistical analysis to identify significant VASARI features in determining glioma grade, IDH mutation, and MGMT methylation status. RESULTS: The study demonstrated substantial observer agreement in VASARI feature evaluation (inter- and intra-observer κ = 0.714 - 0.831 and 0.910, respectively). Patient imaging characteristics varied significantly with glioma grade, IDH mutation, and MGMT methylation. A predictive model was established using VASARI features for glioma grade prediction, exhibiting an AUC of 0.995 (95% CI = 0.986 - 0.998), 100% sensitivity, and 92.86% specificity. IDH mutation status was predicted with AUC 0.930 (95% CI = 0.882 - 0.977), and improved slightly to 0.933 with 'age-at-diagnosis' added. A model predicting MGMT methylation had a satisfactory performance (AUC 0.757, 95% CI = 0.645 - 0.868), improving to 0.791 when 'age-at-diagnosis' was added. CONCLUSIONS: The T1/FLAIR ratio, enhancement quality, hemorrhage, and proportion enhancing predict glioma grade with excellent accuracy. The proportion enhancing, thickness of enhancing margin, and T1/FLAIR ratio are significant predictors for IDH mutation status. Lastly, MGMT methylation is related to the longest diameter of the lesion, edema crossing the midline, and the proportion of the non-enhancing lesion. VASARI MRI features offer non-invasive and accurate predictive models for glioma grade, IDH mutation, and MGMT methylation status, enhancing glioma patient management.

Neuropathy caused by pesticide exposure on farmers in Ngablak District, Magelang, Central Java, Indonesia: An electroneuromyography study.

Uncontrolled and unsafe use of pesticides can lead to acute and chronic toxicity in farmers, with neuropathy being one of the most common symptoms of chronic toxicity. However, the effects of this toxicity on farmers' electroneuromyography (ENMG) are still unclear. To address this, we conducted a cross-sectional study from July to October 2017 in Ngablak District, Magelang, Central Java, Indonesia. Eligible farmers who were exposed to pesticides underwent electrophysiology examinations, as well as additional tests such as physical examination and laboratory testing. We collected general information such as age and work history by interview. In total, 64 farmers were included in this study. Out of these, 44 farmers were found to have polyneuropathy, with 41 of them having motor polyneuropathy and 19 of them having sensory polyneuropathy. Our findings showed that low blood cholinesterase was associated with distal latency prolongation (p-value: 0.014). The group exposed to organophosphate/carbamate pesticides was also significantly associated with prolonged distal latency (p-value: 0.012). However, motor polyneuropathy was significantly associated with chronic exposure to organophosphate/carbamate pesticides (p-value: 0.009) and not with low blood cholinesterase levels (p-value: 0.454). The study concludes that chronic exposure to organophosphate or carbamate pesticides could result in polyneuropathy disease, particularly in the motor system.

Effectiveness and safety of normoxic allogenic umbilical cord mesenchymal stem cells administered as adjunctive treatment in patients with severe COVID-19.

Inflammatory response in COVID-19 contributes greatly to disease severity. Mesenchymal Stem Cells (MSCs) have the potential to alleviate inflammation and reduce mortality and length of stay in COVID-19 patients. We investigated the safety and effectiveness of normoxic-allogenic umbilical cord (NA-UC)-MSCs as an adjunctive treatment in severe COVID-19 patients. A double-blind, multicentric, randomized, placebo-controlled trial involving severe COVID-19 patients was performed from January to June 2021 in three major hospitals across Java, Indonesia. Eligible participants (n = 42) were randomly assigned to two groups (1:1), namely the intervention (n = 21) and control (n = 21) groups. UC-MSCs dose was 1 × 106 /kg body weight on day D0, D3, and D6. The primary outcome was the duration of hospitalization. Meanwhile, the secondary outcomes were radiographical progression (Brixia score), respiratory and oxygenation parameters, and inflammatory markers, in addition to the safety profile of NA-UC-MSCs. NA-UC-MSCs administration did not affect the length of hospital stay of severe COVID-19 patients, nor did it improve the Brixia score or mMRC dyspnoea scale better than placebo. Nevertheless, NA-UC-MSCs led to a better recuperation in oxygenation index (120.80 ± 72.70 baseline vs. 309.63 ± 319.30 D + 22, p = 0.038) and oxygen saturation (97.24 ± 4.10% vs. 96.19 ± 3.75% in placebo, p = 0.028). Additionally, compared to the placebo group, the treatment group had a significantly smaller increase in PCT level at D + 22 (1.43 vs. 12.76, p = 0.011). No adverse effects, including serious ones, were recorded until D + 91. NA-UC-MSCs therapy is a very safe adjunct for COVID-19 patients. It improves the oxygenation profile and carries potential to suppress inflammation.

Association of Pesticide Exposure with Cognitive Function in Farmers.

INTRODUCTION: Organophosphate and carbamate are two types of pesticides that can induce cholinesterase suppression in humans. These lead to poisoning symptoms including muscle paralysis and respiratory depression in acute settings. In chronic settings, the mechanism of organophosphate and carbamate poisoning is still openly discussed. Accordingly, this study aimed to identify any correlations between erythrocyte cholinesterase and type of pesticides with cognitive performance of the subjects. METHODS: This cross-sectional study was conducted in two sampling periods (July 2017 and October 2018) in Ngablak Districts, Magelang Regency, Central Java, Indonesia. The study subjects were farmers with history of pesticide exposure. Cholinesterase levels (ChE) were analyzed from blood samples. Cognitive performance was assessed using the Mini Mental State Examination (MMSE) and Stroop Test. RESULTS: In total, 151 subjects aged between 23 and 91 years old were included. The long-term organophosphate exposure group had significantly lower MMSE scores compared with other types of pesticides, but not in carbamate (p = 0.017). After comparing "organophosphate only" and "carbamate only" groups, there were significant differences in MMSE scores (p = 0.018) but not in blood ChE levels (p = 0.286). Detailed assessment in MMSE domains showed significantly lower scores for orientation, attention, and registration domains (p < 0.05) in the organophosphate group. There were no significant associations between types of pesticides and blood ChE levels with the Stroop Test results (p > 0.05). CONCLUSIONS: Long-term organophosphate exposure could produce lower cognitive function and the insignificant association between blood ChE levels to MMSE could lead to non-cholinergic pathways as its underlying pathology.

Prevalence of pesticide related occupational diseases among Indonesian vegetable farmers - A collaborative work.

Objective: This study was done to understand the prevalence of various occupational diseases including dry eyes, nail dystrophy, and neuropathy related to pesticide exposure in Indonesian local vegetable farmers. Methods: The data were collected through questionnaires and physical examination involving dermatology, neurology, and ophthalmology domains at Ngablak District, Magelang, Central Java directed to local vegetable farmers. Ocular Surface Disease Index (OSDI) questionnaire and the Schirmer test were used. Analysis was done using descriptive statistics using the Statistical Package for the Social Sciences (SPSS 21.0) and presented in tables. Results: Inadequate spraying equipment and improper storage of pesticides were found. Out of 105 farmers, 41.9 % experienced occupational skin diseases (OSD). Definite cognitive impairments were found in 3.4 % of subjects but probable in 28.3 % of subjects. Neuropathies were found in 61.7 % of subjects, and dry-eyes syndrome were found in 28.78 % of subjects. Conclusion: There was a high prevalence of peripheral neuropathy and tremor, dry eyes syndrome in one-third of the population, and the most common skin problem was nail discoloration, with a low incidence of contact dermatitis.

Association of Hormonal Contraception with Meningioma Location in Indonesian Patients.

BACKGROUND: Meningioma is the most common primary intracranial tumor. Previous studies have shown the possible association between hormonal contraceptive use and meningioma location. Therefore, this study aimed to analyze the association between the history of hormonal contraceptive use and the location of meningioma in the Indonesian population. METHODS: In total, 99 histologically confirmed female meningioma patients admitted to Dr. Sardjito General Hospital Yogyakarta, Indonesia, were included in this study. Data on hormonal contraception and other variables were collected from medical records. Meningioma locations were determined from brain Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) scan before surgery. RESULTS: Seventy-two (72.7%) patients had a history of hormonal contraceptive use. The subjects consist of 83 (83.8%) WHO grade I and 16 (16.2%) WHO grade II and III tumors. A total of 57 (57.6%) tumors were located in the spheno-orbital region. We found a significant association between hormonal contraceptive use and meningioma location in the spheno-orbital region (Odds ratio (OR) 2.573, p=0.038). This resulted in the patients in the hormonal contraception group having more visual impairment (p=0.044). CONCLUSION: The use of hormonal contraception is associated with the location of meningioma in the spheno-orbital region.

Mutation spectrum analysis of DMD gene in Indonesian Duchenne and Becker muscular dystrophy patients.

Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the DMD gene. The full mutation spectrum of the DMD gene in Indonesian patients is currently unknown. Mutation-specific therapies are currently being developed, such as exon skipping or stop codon read-through therapy. This study was conducted with the aim of identifying the mutation spectrum of the DMD gene in Indonesia to guide future development and application of feasible therapeutic strategies. Methods: This study is a cross sectional study that enrolled 43 male patients with a clinical suspicion of DMD or BMD. Multiplex ligation-dependent probe amplification (MLPA) reaction was performed to screen for the common mutations in the DMD gene. Results: Out of 43 subjects, deletions accounted for 69.77% (n=30) cases, while duplications were found in 11.63% (n=5) cases. One novel duplication spanning exons 2 to 62 was identified. Deletion mutations clustered around the distal (66.67%) and proximal (26.67%) hot spot regions of the DMD gene while duplication mutations were observed solely at the proximal region. Two false positive cases of single exon deletion detected through MLPA were attributed to sequence mutations affecting primer ligation sites, confirming the need to validate all single exon deletions when using this screening method. Analysis of available maternal DNA samples showed that the rate of de novo mutations (48.15%) appears higher than expected in this population. Out of 31 patients who were classified as DMD based on clinical and genotype characterizations, 60.47% (n=26) of cases were suitable for exon skipping therapy. Conclusion: This is the first comprehensive study showing the feasibility of implementing the MLPA method for routine screening of DMD patients in Indonesia. This is also the first study showing the potential applicability of exon skipping therapy in the majority of DMD cases in the country.

Diagnostic Accuracy of Immunohistochemistry in Detecting MGMT Methylation Status in Patients with Glioma.

BACKGROUND: The O6-methylguanine-DNA methyltransferase (MGMT) gene prevents mismatch in DNA replication and transcription by repairing mutagenic DNA lesions. MGMT is a predictor biomarker of chemotherapy in high-grade and low-grade gliomas based on high-risk clinical conditions. It also can be used for therapeutic decisions to predict hypermutation in recurrence in newly diagnosed low-grade gliomas. The gold standard  examination for the methylation is Polymerase Chain Reaction (PCR). However, this technique is not widely available in Indonesia for daily practice. Thus, an uncomplicated and simpler method such as immunohistochemistry (IHC) is needed as an alternative examination. This study aimed to predict the diagnostic accuracy of immunohistochemistry (IHC) in detecting the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) in glioma. METHODS: This research was a cross-sectional study using formalin-fixed paraffin embedded (FFPE) tissue samples of glioma patients, dating between October 2017 until March 2021. Diagnosis of glioma was established based on clinical, radiological, and histopathological findings. MGMT methylation status was investigated using the IHC and PCR techniques. Diagnostic value of IHC was analyzed, with PCR as a gold standard method. Optimum threshold to determine positivity of IHC was determined by the Area Under the Curve (AUC) on Receiver Operating Characteristics (ROC) curve and Youden index. RESULTS: Among 75 samples examined, 29 (38.7%) patients were methylated. IHC detected MGMT methylation with sensitivity of 86.2%, specificity of 63.0%, positive predictive value of 59.5%, negative predictive value of 87.9% and accuracy of 72.0%. The AUC was 0.746, indicating moderate diagnostic value. Optimum positivity threshold of the IHC examination based on Youden Index was 10%. CONCLUSION: IHC examination can be used to detect MGMT methylation status of glioma patients in limited resources setting, where PCR technique is not available.

Seizure in Indonesian Glioma Patients: Associated Risk Factors and Impact on Survival.

OBJECTIVE: Seizure is commonly found in patients with glioma. This study aimed to find risk factors for seizures in Indonesian patients with glioma. We also sought to determine the association between seizure and survival in this patient population. METHODS: Patients with glioma were enrolled from the Dr. Sardjito General Hospital and other hospitals in Yogyakarta Province, Indonesia. Detailed demographic and clinical data were collected from medical records. DNA extraction and polymerase chain reaction (PCR) were performed to detect IDH1 mutation. Tumor tissue samples were stained by hematoxylin-eosin and classified according to the 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors. Expression of Ki-67 was detected by immunohistochemistry staining. Survival data were also collected. RESULTS: In total, 107 patients were included in the analysis. Age, gender, history of smoking, tumor side, tumor grade, Ki-67 expression, and IDH1 mutation were not associated with seizure. Tumors involving the frontal lobe (p=0.037) and oligodendroglioma histology (p=0.031) were associated with the development of seizures in this study. However, multivariate analysis showed that only oligodendrogial histology was associated with seizure [p=0.032, odds ratio (OR) = 4.77, 95% confidence interval (CI) = 1.146-19.822]. Patients with seizures have significantly longer median overall survival than patients without seizures (69.3±25.01 vs. 10.6±6.14 months, respectively, p=0.04). CONCLUSION: This study showed that seizure in patients with glioma in Indonesia is associated with frontal lobe location and oligodendroglioma histology. Patients with seizures also have significantly longer overall survival. 
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Remarkable response to pericardial window procedure and weekly docetaxel treatment in a metastatic breast cancer patient with pericardial effusion and cardiac tamponade.

Metastatic breast cancer may present as a pericardial effusion that can progress to a life-threatening cardiac tamponade. Pericardial window followed by initial chemotherapy needs to be immediately applied in order to achieve a favorable outcome.

Comparison of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism, Immunohistochemistry, and DNA Sequencing for the Detection of IDH1 Mutations in Gliomas.

BACKGROUND: IDH1 mutation shows diagnostic, prognostic, and predictive value in gliomas. Direct Sanger sequencing is considered the gold standard to detect IDH1 mutation. However, this technology is not available in most neuropathological centers in developing countries such as Indonesia. Immunohistochemistry (IHC) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) have also been used to detect IDH1 mutation. This study aimed to compare DNA sequencing, IHC, and PCR-RFLP in detecting IDH1 mutations in gliomas. METHODS: Research subjects were recruited from Dr. Sardjito Hospital. Genomic DNA was extracted from fresh or formalin-fixed paraffin-embedded samples of tumor tissue. DNA sequencing, PCR-RFLP and IHC were performed to detect IDH1 mutation. Sensitivity, specificity, and accuracy of PCR-RFLP and IHC were calculated by comparing them to DNA sequencing as the gold standard. RESULTS: Among 61 recruited patients, 13 (21.3%) of them carried a mutation in codon 132 of the IDH1 gene, as shown by DNA sequencing. PCR-RFLP and DNA sequencing have a concordance value of 100%. Meanwhile, the concordance value between IDH1 R132H IHC and DNA sequencing was 96.7%. The sensitivity, specificity, positive predictive values, negative predictive values, and accuracy for PCR-RFLP were all 100%. On the other hand, the sensitivity, specificity, and accuracy of IHC were 92.3%, 97.9%, and 96.7%, respectively. CONCLUSION: This study showed that both PCR-RFLP and IHC have high accuracy in detecting IDH1 mutation. We recommend a combination of PCR-RFLP and IHC to detect IDH1 mutation in resource-limited settings.
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Clinicopathological Features and Prognosis of Indonesian Patients with Gliomas with IDH Mutation: Insights into Its Significance in a Southeast Asian Population.

BACKGROUND: Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of clinicopathological profiles. However, the distribution and significance of these mutations have never been studied in the Indonesian population. This study aimed to elucidate the association between IDH mutations and clinicopathological as well as prognostic profiles of Indonesian patients with gliomas. METHODS: In total, 106 patients with gliomas were recruited from a tertiary academic medical center in Yogyakarta, Indonesia. Formalin-fixed paraffin-embedded and fresh tissue specimens were obtained and sectioned for hematoxylin-eosin staining and immunohistochemical examinations. Genomic DNA was isolated and analyzed for the presence of IDH mutations using standard polymerase chain reaction and nucleotide sequencing methods. Clinicopathological data were collected from medical records. RESULTS: Although no IDH2 mutation was identified, IDH1 mutations were found in 23 (21.7%) of the patients. Patients with IDH1 mutations tended to have a history of smoking and a shorter interval between onset of symptoms and initial surgical interventions. Frontal lobe involvement, oligodendroglial histology, lower Ki67 expression, WHO grades II and III gliomas, and methylated O6-methylguanine-DNA methyltransferase (MGMT) promoters were significantly associated with the presence of IDH1 mutations. Compared with patients with IDH1-wild-type, patients with IDH1 mutation were observed to have a longer overall survival. CONCLUSIONS: IDH1 mutations are associated with certain clinicopathological and prognostic profiles in Indonesian patients with gliomas. This finding demonstrates the importance of identifying IDH mutations as part of the management of patients with glioma in Indonesia. 
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Association between Ki-67 Labeling index and Histopathological Grading of Glioma in Indonesian Population.

BACKGROUND: Gliomas are the most frequent primary brain tumors. According to World Health Organization guidelines, gliomas are graded into four groups (Group I-IV). This histological grading will determine prognosis and treatment of the patient. Morphological criteria are not always accurate. Tumor proliferation index is a potent quantitative marker for tumor behavior and prognosis, also it's the basis of gliomagenesis. Ki-67 immunohistochemistry examination for determining proliferation index has been suggested as an ancillary marker in deciding the definitive grading of glioma. OBJECTIVE: To analyze the correlation between Ki-67 labeling index and histopathological grading of glioma in Indonesian population. METHODS: One hundred and six formalin fixed-paraffin embedded tissue of glioma patients were collected from 4 different hospitals. Expression of Ki-67 was detected using immunohistochemistry staining and the labeling index was counted. The association between Ki-67 labeling index and histopathological grading was analyzed. RESULTS: Age range of patient were 1-73-years old, with male predominance (55.70%). Glioblastoma was the most common diagnosis accounting for 41.51% of all samples. Ki-67 labeling index cut point of 6.35% was obtained and significantly sensitive and specific for determining low- or high-grade glioma (p<0.001). CONCLUSION: A significant association between Ki-67 labeling index and histopathological grading in Indonesian glioma patients has been revealed. The result of this study may be used to improve diagnostic and grading accuracy of glioma cases in Indonesia, especially in small biopsy specimens.
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Prevalence of Stroke and Associated Risk Factors in Sleman District of Yogyakarta Special Region, Indonesia.

BACKGROUND: Stroke remains one of the most common noncommunicable diseases among Indonesian populations. This study aimed to identify the prevalence of stroke and its associated risk factors in the Sleman District of Yogyakarta Special Region, Indonesia. METHOD: This study was a secondary analysis of community-based data collected by the Sleman Health and Demographic Surveillance System (HDSS) in 2016. Basic demographic and socioeconomic data were collected. Additional questions about history of stroke and other chronic diseases were interviewed as a self-reported diagnosis. History of hormonal contraceptives use and dietary patterns were also collected. We examined the association between the prevalence of stroke and risk factors, namely, age, gender, self-reported history of chronic diseases, hormonal contraceptives use, and high-risk dietary patterns. RESULTS: The survey included 4,996 households composed of 20,465 individuals. Data regarding stroke incidents were available from 13,605 subjects aged ≥20 years old. Among them, a total of 4,884 subjects also have data regarding stroke risk factors. The overall prevalence of stroke in Sleman District was 1.4% (0.5% men and 0.90% women). The prevalence increased with additional decades of age (p<0.001). In a multivariable model, increasing age, self-reported history of hypertension (OR=8.37, 95%CI: 4.76 to 14.69), and self-reported history of diabetes mellitus (OR=2.87, 95%CI: 1.54 to 5.35) were significantly associated with stroke. CONCLUSIONS: A community-based survey in Indonesia showed a high prevalence of stroke which was associated with increasing age, hypertension, and diabetes mellitus. These findings suggest that preventive actions against the aforementioned modifiable risk factors should be prioritized.

Association between Increased Matrix Metalloproteinase-9 (MMP-9) Levels with Hyperglycaemia Incidence in Acute Ischemic Stroke Patients.

BACKGROUND: Hyperglycemia is common in acute stroke patients. Hyperglycemia can induce the production of reactive oxygen species, causing increased activity of matrix metalloproteinase-9 (MMP-9). AIM: This study aimed to determine an association between the increased levels of MMP-9 and the incidence of hyperglycemia in acute ischemic stroke patients. METHODS: This is a case-control study. Acute ischemic stroke patients admitted to the Stroke Unit of a reference hospital in Yogyakarta, Indonesia was divided into the hyperglycemic and non-hyperglycemic group. Demographic and clinical characteristics of each subject were recorded, and blood levels of MMP-9 were measured. Seventy-one patients were recruited, 40 subjects in the hyperglycemic group and 31 subjects in the non-hyperglycemic group. RESULTS: The median levels of blood MMP-9 level in the hyperglycemic and non-hyperglycemic group were 974.37 and 748.48 ng/mL, respectively, and the difference was statistically not significant (95% CI, 191.24-2849.53; p = 0.07). When the calculated cut-off point of 600.99 ng/mL was used, the proportion of patients with higher MMP-9 levels was significantly more in the hyperglycemic group compared with the ones in the non-hyperglycemic group (82.5% and 54.8%, respectively; OR = 3.88; p = 0.011). CONCLUSION: We concluded that the proportion of patients with MMP-9 level >600.99 ng/mL was significantly higher in acute ischemic stroke patients with hyperglycemia.

The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with worse functional outcome of ischaemic stroke.

PURPOSE: Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be associated with the occurrence of ischaemic stroke through its effect on pathogenesis of atherosclerosis and hypertension. This study was aimed to examine the association between this polymorphism with functional outcome of ischaemic stroke. METHOD: This was a cross-sectional study. The subjects were patients with ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on demographic characteristics, stroke risk factors, comorbidities and stroke severity were assessed on admission. The functional outcome, Barthel index (BI), was assessed when the patients were discharged from the hospital. ACE I/D genotypes of the patients were identified by polymerase chain reaction (PCR). RESULT: In total, 61 patients were included. Of these, 38 patients (62.3%) had II polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD polymorphism in the ACE gene. There were significant differences in the functional outcomes between patients without D allele (II polymorphisms) and patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 ± 23.57 and 60.65 ± 27.15, respectively; p = 0.034). Multiple linear regression model showed that the availability of D allele is an independent variable negatively associated with functional outcome as assessed by BI (ß = -0.232, p = 0.024). CONCLUSION: This study showed that the D allele in ACE I/D polymorphism is associated with worse functional outcomes. This highlights the possibility of further research to improve functional outcomes of ischaemic stroke by inhibiting the ACE system.

Histopathological Features of Lymphoma in Yogyakarta, Indonesia.

The incidence and prevalence, the second most common lymphoid malignancy after leukemia, are both increasing. The distribution of lymphoma varies among sexes, age groups, and sites. In Indonesia, information about the incidence of lymphoma and its characteristics are insufficient. Therefore, this study was performed to evaluate the incidence of lymphoma and features based on age group, sex, site, clinical diagnosis, and histopathological type in Indonesia. This study is an observational analytical study with a cross-sectional design aimed to evaluate the histopathological profile of lymphoma in Yogyakarta from 2010-2014. It was based on secondary data from Anatomic Pathology Department's medical records from several hospitals and laboratories. The result showed an increased incidence of lymphoma in Yogyakarta in 2010-2014 (p=0.039). Lymphoma mostly occurred in age range 45-64 years (p=0.004), dominated by male with ratio 1.6:1. DLBCL was found to be the most common histopathological type (44.4%). Sex, age, and clinical diagnosis demonstrated statistically significant correlations with the histopathological type (p<0.001). In conclusion, the incidence of lymphoma has significantly increased from 2010-2014. There are statistically significant correlations between gender, age, and clinical diagnosis with the histopathological type of lymphoma.

Effectiveness of Gotu Kola Extract 750 mg and 1000 mg Compared with Folic Acid 3 mg in Improving Vascular Cognitive Impairment after Stroke.

This study aimed to determine the effectiveness of gotu kola (Centella asiatica) in improving cognitive function in patients with vascular cognitive impairment (VCI). This study uses a quasi-experimental design. Subjects in this study were patients with poststroke cognitive impairment who were treated at two hospitals in Yogyakarta, Indonesia. The number of subjects was 48: 17 subjects were treated with 1000 mg/day of gotu kola extract, 17 subjects treated with 750 mg/day of gotu kola extract, and 14 subjects treated with 3 mg/day of folic acid for 6 weeks. A Montreal Cognitive Assessment-Indonesian version (MoCA-Ina) was conducted at the beginning of treatment and after 6 weeks of therapy. It was found that all trials effectively improved poststroke VCI based on MoCA-Ina scores over the course of the study. There is no significant difference in ΔMoCA-Ina (score at the 6th week of treatment - score at the beginning) mean score among the three groups, indicating that gotu kola is as effective as folic acid in improving poststroke VCI. Gotu kola was shown to be more effective than folic acid in improving memory domain. This study suggested that gotu kola extract is effective in improving cognitive function after stroke.

Phosphorothioate modification of chimeric 2´-O-methyl RNA/ethylene-bridged nucleic acid oligonucleotides increases dystrophin exon 45 skipping capability and reduces cytotoxicity.

BACKGROUNDS: Antisense oligonucleotide (AO)-mediated exon skipping is the most promising way to express internally deleted dystrophin in Duchenne muscular dystrophy (DMD), by correcting the reading frame of dystrophin mRNA. An antisense chimeric oligonucleotide consisting of 2´-O-methyl RNA and ethylene-bridged nucleic acid (ENA), targeting exon 45 of the dystrophin gene, AO85, has been shown to induce exon 45 skipping efficiently. Since phosphorothioate (PS)-modification of AO85 has never been explored, we produced a PS-modified AO85 (AO88) and examined its exon skipping capability and cytotoxicity. METHODS: Exon 45 skipping activity was examined in primary muscle cells established from a DMD patient carrying a deletion of dystrophin exon 44. Cytotoxicity was assessed by MTT assay. RESULTS: AO88 induced dystrophin exon 45 skipping from 50 nM. More than 90% of products lacked exon 45 at 400 nM. AO88 showed significantly higher exon skipping activity than AO85. The EC50 of AO88 was 94.8 nM, while EC50 of AO85 was 66.7 nM. Cytotoxicity was lower for AO88 than for AO85. CONCLUSION: the PS-modified RNA/ENA chimera displayed stronger exon skipping activity and lower cytotoxicity than the phosphodiester-RNA/ENA chimera. AO88 has better potential for clinical use than AO85.