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.

Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors.

BACKGROUND: Obesity and other metabolic comorbidities affect over 10% of patients with breast cancer and are closely related with adverse outcomes. Although metabolic comorbidities among breast cancer patients in low- and middle-income countries are suggested to be lower, only a few studies are currently available. Effective management of metabolic comorbidities in cancer patients has been associated with better outcomes. METHODS: Non-metastatic breast cancer patients (N = 1081) treated in our department (2014-2018) were monitored for the presence of high Body Mass Index (BMI), diabetes or glucose intolerance, dyslipidemia, and hypertension and the development of recurrent metastatic diseases during a median follow-up of 3.9 years. RESULTS: Glucose intolerance, hypertension, dyslipidemia, and BMI ≥ 27.7 kg/m2 considered at risk for metabolic comorbidities were found in 26.5, 42.6, 27.7, and 23.3% of breast cancer patients, respectively. Diabetes or glucose intolerance and having both glucose intolerance and dyslipidemia were associated with the risk of recurrent metastatic disease (OR = 1.442, 95%CI = 1.071-1.943, p = 0.016 and OR = 1.495, 95%CI = 1.090-2.049, p = 0.010; respectively). Having three or more metabolic comorbidities was significantly associated with the risk of recurrent metastatic disease (OR = 1.647, 95%CI = 1.139-2.382, p = 0.008) compared to patients without any comorbidity. The metabolic comorbidities were distributed unevenly among breast cancer subtypes. A significant association with recurrent metastatic disease was found in the Luminal B-like subtype. In post-menopausal patients, having more than three comorbidities was associated with a higher risk of recurrent metastatic disease compared to those without any comorbidity (OR = 2.000, 95%CI = 1.035-3.067, p = 0.001). The risks of having three or more metabolic comorbidities were significantly higher in breast cancer survivors who were obese, lived in an urban area, and received hormonal therapy of aromatase inhibitors. CONCLUSION: Metabolic comorbidities were frequently found in breast cancer patients and were associated with higher risks to develop recurrent metastatic disease, particularly in post-menopausal women. Subsequent larger studies are needed to better understand the association of metabolic comorbidities with patients' quality of life and prognosis, and to explore the potential combination of clinical intervention and lifestyle modification in breast cancer survivors to treat as well as reduce their impact.

Risk factors of distant metastasis after surgery among different breast cancer subtypes: a hospital-based study in Indonesia.

BACKGROUND: More than one third of breast cancer patients including those that are diagnosed in early stages will develop distant metastasis. Patterns of distant metastasis and the associated risks according to the molecular subtypes are not completely revealed particularly in populations of patients with delayed diagnosis and advanced stages. METHODS: Breast cancer patients (n = 1304) admitted to our institute (2014-2017) were evaluated to identify the metastatic patterns and the associated risks. Metastatic breast cancers at diagnosis were found in 245 patients (18.7%), and 1059 patients were then grouped into non-metastatic and metastatic groups after a median follow-up of 3.8 years. RESULTS: Infiltration of the tumor to the skin and chest wall prevailed as the most powerful predictor for distant metastasis (OR 2.115, 95% CI 1.544-2.898) particularly in the luminal A-like subtype (OR 2.685, 95% CI 1.649-4.371). Nodal involvement was also significantly associated with the risk of distant metastasis (OR 1.855, 95% CI 1.319-2.611), and the risk was higher in the Luminal A-like subtype (OR 2.572, 95% CI 1.547-4.278). Luminal A-like subtype had a significant higher risk of bone metastasis (OR 1.601, 95% CI 1.106-2.358). In respect to treatment, a combination of anthracyclines and taxanes-based chemotherapy was significantly associated with lower distant organ spread in comparison with anthracycline-based chemotherapy (OR 0.510, 95% CI 0.355-0.766) and the effect was stronger in Luminal A-like subtype (OR 0.417, 95% CI 0.226-0.769). Classification into Luminal and non-Luminal subtypes revealed significant higher risks of bone metastasis in the Luminal subtype (OR 1.793, 95% CI 1.209-2.660) and pulmonary metastasis in non-Luminal breast cancer (OR 1.445, 95% CI 1.003-2.083). CONCLUSION: In addition to guiding the treatment plan, a comprehensive analysis of clinicopathological variables including the molecular subtypes could assist in the determination of distant metastasis risks of breast cancer patients. Our study offers new perspectives concerning the risks of distant metastasis in breast cancer subtypes in order to plan intensive surveillance or escalation of treatment particularly in a setting where patients are predominantly diagnosed in late stages.

Pathological profiles and clinical management challenges of breast cancer emerging in young women in Indonesia: a hospital-based study.

BACKGROUND: Breast cancer diagnosed at a young age is often associated with aggressive biology, advanced stage, and unfavorable prognosis. The median age of breast cancer diagnosis in Indonesia is younger (48 vs. 68 years-old in Europe) with a relatively higher proportion of patients younger than 40 years old. Although prognosis and outcome of young breast cancer are well studied in developed nations, research evaluating biological characteristics, delivered treatment, and clinical outcomes is very limited in Indonesia. METHODS: We analyzed all breast cancer patients who underwent surgery at Dr. Sardjito Hospital, Indonesia, in 2012-2017. Details of pathology profiles, treatment administrated, and outcomes, as well as reproductive factors among patients younger than 40 years old, were collected and analyzed. Kaplan-Meier curve was used to assess conditional survival based on baseline characteristics. RESULTS: From the total of 1259 breast cancer patients (median age 51 years), 144 (11.4%) were younger than 40 years old (median age 37 years). Of these young patients, 19 (13.2%) were bilateral and 92 (64%) were diagnosed in advanced stages (stages IIIA-C and IV). Median tumor diameter was 5.5 cm and nodal infiltration was present in 73%. Distant metastasis was found in 16% at the time of diagnosis. Moderate and poor differentiation of tumor were 20.8 and 78.5%, respectively, and lymphovascular invasion was found in 90.3%. Around 40% were hormone receptor-positive, 30.6% human epidermal growth factor receptor 2 positive, and 38.2% triple negative. Patients underwent radical surgery in 121 cases (84%) and breast conserving surgery in 7 cases (4.9%). Adjuvant chemotherapy was administrated in 68% and hormonal therapy in 34%. Progression-free survival was significantly shorter in patients with advanced stage, skin and chest wall involvement (T4), positive lymph node infiltration, positive hormonal receptor, and triple negative subtype (log-rank Mantel-Cox tests, p < 0.05). CONCLUSION: We found a high frequency of young breast cancer with biologically more aggressive tumors, late diagnosis, frequent relapse, and poor prognosis. Further actions to improve clinical management and meet psychosocial needs in young breast cancer patients are warranted.

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.

A novel splicing silencer generated by DMD exon 45 deletion junction could explain upstream exon 44 skipping that modifies dystrophinopathy.

Duchenne muscular dystrophy (DMD), a progressive muscle-wasting disease, is mostly caused by exon deletion mutations in the DMD gene. The reading frame rule explains that out-of-frame deletions lead to muscle dystrophin deficiency in DMD. In outliers to this rule, deletion junction sequences have never previously been explored as splicing modulators. In a Japanese case, we identified a single exon 45 deletion in the patient's DMD gene, indicating out-of-frame mutation. However, immunohistochemical examination disclosed weak dystrophin signals in his muscle. Reverse transcription-PCR amplification of DMD exons 42 to 47 revealed a major normally spliced product with exon 45 deletion and an additional in-frame product with deletion of both exons 44 and 45, indicating upstream exon 44 skipping. We considered the latter to underlie the observed dystrophin expression. Remarkably, the junction sequence cloned by PCR walking abolished the splicing enhancer activity of the upstream intron in a chimeric doublesex gene pre-mRNA in vitro splicing. Furthermore, antisense oligonucleotides directed against the junction site counteracted this effect. These indicated that the junction sequence was a splicing silencer that induced upstream exon 44 skipping. It was strongly suggested that creation of splicing regulator is a modifier of dystrophinopathy.

A renal aplasia case mimicking radiologically as unilateral renal agenesis in a child with spina bifida, atresia ani and unilateral undescended testis: a case report.

BACKGROUND: As a result of the failure of embryogenic kidney formation, a condition can occur where not a single kidney appears and this phenomenon is known as unilateral renal agenesis (URA). Both aplastic and dysplastic kidney are different from renal agenesis, atrophy and renal hypoplasia. However, from this case report it can be seen that there are similarities, both radiologically and macroscopically, between cases of unilateral renal aplasia and renal agenesis. CASE PRESENTATION: A 2 year old Javanese boy came to the health facility with complaints of recurrent fever and urinary tract symptoms such as dysuria and straining. Computerized Tomography (CT) scan of the abdomen and urography showed agenesis of the left kidney and a probable spina bifida. Cystourethrography examination was done and showed grade 5 voiding, then retrograde pyelography was performed with the diagnosis of unilateral renal agenesis was made because there was no visible left side collecting system even though there was a duplication in the left ureter. The next examination was carried out by histopathology and immunohistochemistry after resection of the left side of the ureter and the diagnosis increasingly pointed towards renal aplasia after primitive renal structures were found. CONCLUSIONS: Renal agenesis and aplastic kidney are difficult to differentiate macroscopically and radiologically. Nevertheless, from this case report, we try to provide some interesting points to differentiate cases of unilateral renal agenesis from Renal Dysplasia which presents as unilateral renal aplasia.

High P16INK4A Expression, Keratinizing Features, and Surgical Margin-Free Status are Associated with Improved Survival in Patients with Oral Squamous Cell Carcinomas.

BACKGROUND: Oral squamous cell carcinoma (OSCC) continues to prevail as a highly prevalent cancer in Southeast Asia and causes a significant health burden. Stratification of patients with high risks of recurrence and mortality is important in the planning of treatment and surveillance. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissues of OSCC were immuno-stained and analyzed for p16 expression. Risk factors and clinical parameters of OSCC patients were collected and compared to identify factors associated with recurrences and overall survival. RESULTS: After a median follow-up of 32 months, OSCC recurrences and mortality were observed in 82% and 78% of patients (N=60), respectively. Larger and more extensive tumors (T3 and T4) were significantly associated with both recurrences and cancer-associated mortality (OR = 3.967, 95% CI = 1.007-15.618 and OR = 5.885, 95% CI = 1.541-22.47, respectively). P16INK4A positive staining was found in 31% of tumors. Patients with p16INK4A positive staining were significantly associated with better recurrence-free and overall survivals (medians of recurrence-free survivals were 31.2 vs 19.0 months, P=0.038 and overall survivals were 39.0 vs 28.8 months,  P=0.048; respectively). Some other clinical characteristics including early stages, non-keratinizing tumors, negative cervical node, and free-surgical margin were significantly associated with better recurrence-free and overall survivals (log-rank tests, P<0.05). CONCLUSION: P16INK4A positive staining, early stages, negative cervical lymph node infiltration, and free-surgical margins are associated with better prognosis in OSCC patients. The study emphasizes the importance of early detection and the potential use of p16INK4A and other clinical variables to stratify OSCC patients with high risks of recurrence and worse overall survivals.

Isolated skeletal Langerhans cell histiocytosis in adults: A case report.

INTRODUCTION AND IMPORTANCE: LCH in adults is rarely encountered, with the preference in children and axial skeleton as predilection site. Limited understanding of adult LCH causes frequent misdiagnosis, as our experience in an adult case of LCH threw off our differential diagnosis. CASE PRESENTATION: A 21-year-old male was referred to our hospital due to pain in his right shoulder. Plain radiograph and MRI showed a solitary well-marginated lytic lesion on the distal third of the clavicle. Together with a clear history and physical exam, the benign bone cyst was suspected and we performed an open biopsy simultaneously with curettage followed by internal fixation using a bone graft. Pathology and immunohistochemistry dismissed our suspicion and confirmed LCH as the main diagnosis. At six months post-surgery, no signs of recurrence were seen on the fixated site nor complained by the patient. DISCUSSION: Diagnosing LCH involves considering imaging appearances and patient demographics as initial clues. However, confirming the diagnosis requires a biopsy with proven CD1 expression. Currently, the majority of studies recommend confirming the diagnosis before initiating therapy. This precaution is necessary due to the unclear pathophysiology of LCH, which complicates the implementation of specific therapies. Based on benign features of skeletal lesions found from imaging, invasive treatment before biopsy confirmation still gave a satisfactory outcome despite not being in line with the current recommendation. CONCLUSION: Excisional biopsy and curettage in solitary LCH yield satisfactory outcomes. However, further studies are needed with larger sample sizes and interventional designs.

Tumor Infiltrating Lymphocytes as an Independent Prognostic Factor in Undifferentiated Nasopharyngeal Carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common type of cancer in Southeast Asia. This cancer usually spreads locally and to nearby lymph nodes. One unique feature of NPC is its many immune cells called tumor-infiltrating lymphocytes (TILs). Recent studies have suggested that TILs in many types of cancer can indicate a better prognosis. However, the role of TILs in NPC is still a matter of debate. Further research is necessary to determine whether TILs can be used as a prognostic factor of NPC's outcome. METHOD: A retrospective cohort study was conducted at Sardjito Hospital to examine the records and pathological sections of patients treated for the undifferentiated subtype of NPC. Two pathologists analyzed the presence of TILs using HE-stained slides. TILs were evaluated in stromal compartments, and their association with clinicopathological variables was analyzed using the Chi-square and Fisher exact tests. The study compared overall survival in tumor patients with varying TIL levels using Kaplan-Meier survival curves and the log-rank test. A Cox regression model was used for univariate and multivariate analyses to test the significance of different factors. RESULT: Out of the total 61 subjects, 16 (26.2%) had high stromal TILs (≥ 70%), and 45 (73.8%) had low stromal TILs (<70%). The subjects' sex, age, and tumor stage did not affect the OS. However, high stromal TILs (≥ 70%) showed a significant association with a longer OS (log-rank test p = 0.006, HR 0.37, 95% CI 0.17-0.79, log-rank p = 0.006). Moreover, multivariate analysis confirmed that TILs were an independent prognostic indicator for OS (aHR 0.015). CONCLUSION: TILs correlate positively with overall survival in the undifferentiated NPC subtype and are an independent prognostic indicator.

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.

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.

Right Thigh Mass Metastasis from Lung Cancer Mimicking Primary Soft Tissue Sarcoma: A Case Report.

BACKGROUND Soft tissue metastases (STMs) are less common than bone metastases and sometimes misdiagnosed as primary soft tissue malignancies. Skin, lungs, and breast are the most common primary lesions of STMs and rarely the presenting symptoms. We present an STM from lung adenocarcinoma that became a presenting symptom in nonsmoking woman. CASE REPORT A 47-year-old woman presented to our hospital with a painful mass in her right thigh and weight loss of 10 kg for 4 months. Femoral radiograph revealed a lesion suggestive of bone sarcoma. However, magnetic resonance imaging (MRI) showed it was more likely a primary soft tissue sarcoma. A small mediastinal mass was noticed on preoperative chest radiograph, and the patient denied any symptoms except the mass in the right thigh. Our clinicopathological conference team decided to perform a biopsy of mediastinal and right thigh masses. Histopathology examinations confirmed the right thigh mass as soft tissue metastasis from mediastinal mass, confirmed as lung adenocarcinoma. We treated the patient with palliative care with zoledronic acid and gefitinib. At the 6-month follow-up, the patient's symptoms significantly improved, and MRI showed a marked size reduction. CONCLUSIONS Diagnosis of STM can be difficult when presenting as the primary manifestation. Failure to identify promptly can lead to rapid disease progression and unfavorable prognosis. Failure to diagnose primary malignancy during biopsy occurs in approximately 28% of cases. This report has the potential to facilitate the avoidance of unnecessary procedures and highlight the importance of using a multidisciplinary approach in managing cases with malignancy.

Classic and rare manifestations of multiple osteoma: A case report.

INTRODUCTION AND IMPORTANCE: Osteoma is a benign tumor that can arise from compact or cancellous bone and is more commonly found in the face or skull. The incidence of osteoma believed to be underreported as most are asymptomatic. To date, the best modality to diagnose osteoma is CT scan. We report a unique case of osteoma presenting with cranial and extracranial manifestations and highlight the importance of bone survey in evaluating patients with osteoma. CASE PRESENTATION: A 26-year-old female complained of bilateral pain in the jawbone and several areas of her head. On physical examination, there were several masses in the head with the largest on the left mandible measuring 5.6 × 6.0 × 4.5 cm from MSCT examination. Hemi-mandibulectomy, histopathological and cytopathology examination were performed on the tissue obtained from the left mandible which concluded osteoma. Post-operative bone survey was performed and found osteoma on left ulna and bilateral fibula. Suspected Gardner syndrome with multiple osteoma manifestation was excluded from normal results of colon in-loop examination. We conservatively monitored the patient and most recent 6-month follow-up found no complaint nor changes in the extracranial osteoma manifestation on left ulna and both fibulas. CLINICAL DISCUSSION: The benign tumor osteoma is incredibly uncommon to present both intra and extracranially. We suggest thorough skeletal studies such as bone survey to be performed as they are crucial in the full evaluation of patients with multiple osteomas. Osteoma treatment is based on the patient's symptoms, surgery for patients with symptoms and periodic monitoring for asymptomatic patients. CONCLUSION: It is necessary to consider radiological modality for diagnosing osteoma patients. The majority of osteomas are asymptomatic and the choice of radiological examination sometimes still misses the lesion. It is important to evaluate histologically if the lesion difficult to diagnose.

Prognostic Value of Vimentin in Triple Negative Breast Cancer Patients Depends on Chemotherapy Regimen and p53 Mutant Expression.

Purpose: To determine the prognostic value of vimentin in triple negative breast cancer (TNBC) patients, specifically in relation to chemotherapy regimen and p53 mutant expression. Patient and Methods: We retrospectively analyzed the association of pre-treatment tumor expression of vimentin with 48-month overall survival (OS) of 72 all stages TNBC patients diagnosed between 2014 and 2018 in relation to chemotherapy regimen and expression of p53 mutant. Vimentin and p53 mutant expressions were examined using immunohistochemistry. Analysis was conducted on all patients collectively, then repeated on two cohorts divided according to the chemotherapy regimen. Sub-analysis was performed to determine the effect of p53 mutant expression on the prognostic value of vimentin. Results: Vimentin was expressed in 43.1% of patients and was not associated with clinicopathologic characteristics. Vimentin was associated with improved 48-month OS in all patients in univariate analysis but not significant in multivariate analysis. When analyzed according to chemotherapy regimen, vimentin was independently associated with improved 48-month OS in patients receiving non-platinum-based chemotherapy (80% vs 15.8%; HR: 0.17, 95% CI: 0.05-0.58, p: 0.005). Other independent prognostic factors include T (HR: 6.18, 95% CI: 1.38-27.7, p: 0.017) and M (HR: 5.64, 95% CI: 1.2-26.33, p: 0.028). On subanalysis, vimentin was significantly associated with improved 48-month OS in patients expressing p53 mutant (69.2% vs 22.2%, p: 0.006) but was not significant in patients not expressing p53 mutant. Conclusion: Vimentin expression was independently associated with improved 48-month OS in TNBC patients treated with non-platinum-based chemotherapy. Expression of p53 mutant significantly affected the prognostic value of vimentin.

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.

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.

Categorization of 77 dystrophin exons into 5 groups by a decision tree using indexes of splicing regulatory factors as decision markers.

BACKGROUND: Duchenne muscular dystrophy, a fatal muscle-wasting disease, is characterized by dystrophin deficiency caused by mutations in the dystrophin gene. Skipping of a target dystrophin exon during splicing with antisense oligonucleotides is attracting much attention as the most plausible way to express dystrophin in DMD. Antisense oligonucleotides have been designed against splicing regulatory sequences such as splicing enhancer sequences of target exons. Recently, we reported that a chemical kinase inhibitor specifically enhances the skipping of mutated dystrophin exon 31, indicating the existence of exon-specific splicing regulatory systems. However, the basis for such individual regulatory systems is largely unknown. Here, we categorized the dystrophin exons in terms of their splicing regulatory factors. RESULTS: Using a computer-based machine learning system, we first constructed a decision tree separating 77 authentic from 14 known cryptic exons using 25 indexes of splicing regulatory factors as decision markers. We evaluated the classification accuracy of a novel cryptic exon (exon 11a) identified in this study. However, the tree mislabeled exon 11a as a true exon. Therefore, we re-constructed the decision tree to separate all 15 cryptic exons. The revised decision tree categorized the 77 authentic exons into five groups. Furthermore, all nine disease-associated novel exons were successfully categorized as exons, validating the decision tree. One group, consisting of 30 exons, was characterized by a high density of exonic splicing enhancer sequences. This suggests that AOs targeting splicing enhancer sequences would efficiently induce skipping of exons belonging to this group. CONCLUSIONS: The decision tree categorized the 77 authentic exons into five groups. Our classification may help to establish the strategy for exon skipping therapy for Duchenne muscular dystrophy.

Cold abscess as a primary manifestation of thyroid tuberculosis.

Tuberculosis remains the highest cause of infection-related mortality in low- and middle-income countries. Extra-pulmonary tuberculosis is often misdiagnosed because of the nonspecific clinical presentations and gaps in the laboratory assessment. Delayed and misdiagnosis can cause increased risks of morbidity and potential community transmission. Primary thyroid tuberculosis is very rare presentation even in the endemic area. We presented a Case Illustrated of a patient with cold abscess as a primary presentation of thyroid tuberculosis. Difficulty in the diagnosis and treatment were described. Although very rare, atypical presentation of extra-pulmonary tuberculosis in the thyroid gland requires thorough anamnesis and in-depth examination. Clinicians should put high-index suspicion on high-risk patients from endemic areas with medical comorbidity including immunocompromised disease and poor nutritional status. Our report underlines the importance of thorough medical assessment for unusual presentation of thyroid tuberculosis.

Hemi-mandibulectomy without bony reconstruction: A case report of mandibular metastasis from a silent differentiated papillary thyroid cancer.

INTRODUCTION: Distant spread to the jaw is a rare metastatic manifestation from papillary thyroid cancer. Complete resection of tumor extension in the facial and oral regions requires consideration to compromise mastication functioning and facial aesthetics. Current advances in the microvascular surgery have facilitated excellent restoration of patient's functioning. Inadequate expertise, facility, longer surgery time and inpatient care, and healthcare insurance disbursement are common challenges in developing countries to perform microvascular surgery. CASE PRESENTATION: A 54-year female presented in an oncology clinic with a rapid progressive lump in the jaw without inflammatory signs. CT-scan revealed a 5.9x5.3 × 5cm lesion with osteo-destruction in the left mandible body. Biopsy was performed indicating a papillary adenocarcinoma invasion. Neck sonography showed hypoechoic nodule with regular border in the thyroid lobes. Fine-needle aspiration biopsy revealed benign follicular cells with Bethesda class II. Total thyroidectomy with frozen section and left hemi-mandibulectomy without bony reconstruction were then performed. Histopathological examination showed papillary thyroid cancer with follicular variant in the thyroid and mandible lesion. Thyroid ablation, TSH suppression, and chewing rehabilitation programs were accomplished by the patient. DISCUSSION: Partial mandibulectomy without bony reconstruction might be an option for selected patients with careful consideration from multidisciplinary team members in which extensive surgery with immediate bony reconstruction is not possible.