Geranylgeraniol Inhibits Lipopolysaccharide-Induced Inflammation in Mouse-Derived MG6 Microglial Cells via NF-κB Signaling Modulation.

Persistent inflammatory reactions in microglial cells are strongly associated with neurodegenerative pathogenesis. Additionally, geranylgeraniol (GGOH), a plant-derived isoprenoid, has been found to improve inflammatory conditions in several animal models. It has also been observed that its chemical structure is similar to that of the side chain of menaquinone-4, which is a vitamin K2 sub-type that suppresses inflammation in mouse-derived microglial cells. In this study, we investigated whether GGOH has a similar anti-inflammatory effect in activated microglial cells. Particularly, mouse-derived MG6 cells pre-treated with GGOH were exposed to lipopolysaccharide (LPS). Thereafter, the mRNA levels of pro-inflammatory cytokines were determined via qRT-PCR, while protein expression levels, especially the expression of NF-κB signaling cascade-related proteins, were determined via Western blot analysis. The distribution of NF-κB p65 protein was also analyzed via fluorescence microscopy. Thus, it was observed that GGOH dose-dependently suppressed the LPS-induced increase in the mRNA levels of Il-1ß, Tnf-α, Il-6, and Cox-2. Furthermore, GGOH inhibited the phosphorylation of TAK1, IKKα/ß, and NF-κB p65 proteins as well as NF-κB nuclear translocation induced by LPS while maintaining IκBα expression. We showed that GGOH, similar to menaquinone-4, could alleviate LPS-induced microglial inflammation by targeting the NF-kB signaling pathway.

Menaquinone-4 Suppresses Lipopolysaccharide-Induced Inflammation in MG6 Mouse Microglia-Derived Cells by Inhibiting the NF-κB Signaling Pathway.

The overactivation of microglia is known to trigger inflammatory reactions in the central nervous system, which ultimately induce neuroinflammatory disorders including Alzheimer's disease. However, increasing evidence has shown that menaquinone-4 (MK-4), a subtype of vitamin K2, can attenuate inflammation in the peripheral system. Whereas it was also observed at high levels within the brain, its function in this organ has not been well characterized. Therefore, we investigated the effect of MK-4 on microglial activation and clarified the underlying mechanism. Mouse microglia-derived MG6 cells were exposed to lipopolysaccharide (LPS) either with or without MK-4 pretreatment. Cell responses with respect to inflammatory cytokines (Il-1ß, Tnf-α, and Il-6) were measured by qRT-PCR. We further analyzed the phosphorylation of TAK1, IKKα/ß, and p65 of the NF-κB subunit by Western blotting. We observed that in LPS-induced MG6 cells, MK-4 dose-dependently suppressed the upregulation of inflammatory cytokines at the mRNA level. It also significantly decreased the phosphorylation of p65, but did not affect that TAK1 and IKKα/ß. Furthermore, the nuclear translocation of NF-κB in LPS-induced MG6 cells was inhibited by MK-4. These results indicate that MK-4 attenuates microglial inflammation by inhibiting NF-κB signaling.

Extraskeletal Ewing's sarcoma presenting as a mediastinal mass with vena cava superior syndrome: A rare case report.

INTRODUCTION: Extraskeletal Ewing's Sarcoma is a rare entity of sarcoma that develops rapidly within soft tissue in any anatomic region, and the symptoms depend on its location. CASE PRESENTATION: The X-ray examination of a 28-year-old man with shortness of breath, cough, weight loss, and chest pain showed malignant round cell, in which confirmed by immunohistochemical examination. The examination indicated positive Vimentin findings in the cytoplasm and positive FLI-1 in the nuclei of the tumour cells. The diagnosis was consistent with extraskeletal Ewing's sarcoma. The patient submitted to a chest conference and received radiotherapy related to SVCS before debulking surgery. DISCUSSION: The diagnostic challenges associated with Ewing's sarcoma may arise due to its diverse histological spectrum. Further examination is required in order to distinguish Ewing's sarcoma from other tumours, as its radiological specificity is limited. A multimodal approach for treatment and therapy is necessary to highlight the specific requirements of the patient's condition. CONCLUSION: Imaging modalities including X-rays and thoracic CT scans, supported by histopathological examination and immunohistochemistry, are essential for accurately diagnosing Extraskeletal Ewing's sarcoma. A multimodal approach may be considered as the best treatment for the patient with mediastinal Ewing's sarcoma.

Exploring the Interaction between Physical, Psychosocial, and Neck Pain Symptoms in Construction Workers.

OBJECTIVE: Construction workers are significantly vulnerable to musculoskeletal disorders, yet the number of studies conducted in developing nations-where these workers significantly contribute to the economy-remains insufficient. This study aims at exploring the interaction between physical and psychosocial exposure to the onset of neck pain or symptoms amongst construction workers in a developing country. METHODS: Using a cross-sectional study design, a total of 235 respondents from various construction projects participated in this study. Participants were assigned into one of four exposure groups: low physical and low psychosocial (which served as the reference group); low physical and high psychosocial; high physical and low psychosocial, and high physical and high psychosocial. To quantitatively assess the interaction, we calculated the relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: Workers experiencing high levels of both physical and psychosocial risk factors had the highest odds ratio (OR) of neck symptoms (OR: 12.63, 95% confidence interval (CI): 3.39 - 46.99) compared to other groups. The AP (AP: 0.33, 95% CI: -0.24 - 0.90), RERI (RERI: 0.40, 95% CI: -0.99 - 1.79), and SI (SI: 1.69, 95% CI: -1.77 - 5.15) revealed an interaction between physical and psychosocial factors that increases the OR of neck symptoms. CONCLUSIONS: This result suggests that physical risk factors at work become significantly more detrimental when paired with high psychosocial stress. Hence, ergonomic interventions in the construction industry aiming to reduce musculoskeletal disorders should consider both physical and psychosocial risk factors concurrently.

Correlation between interleukin-6 expression in post-mortem core liver biopsy and degree of liver injury in patients with fatal COVID-19.

Excessive release of interleukin-6 (IL-6) during the progression of coronavirus disease 2019 (COVID-19) induces cytokine storms, resulting in multi-organ damages including liver injury, similar in nature with mechanism of viral hepatitis. Systemic IL-6 has been associated with the incidence of liver injury among COVID-19 patients; however, studies on IL-6 expression in the liver tissue are completely lacking. The aim of this study was to measure the IL-6 expression in the liver tissues and to determine its correlation with the degree of liver injury in fatal COVID-19 patients. Through this first cross-sectional study, IL-6 expression was measured through immunohistochemical staining and the degree of liver injury was identified based on level of serum alanine aminotransferase (ALT). The Spearman correlation test was used to identify the correlation between IL-6 expression and the degree of liver injury. A total of 47 deceased COVID-19 patients were included and IL-6 expression was observed in all post-mortem liver specimens, ranging from mild to strong expression. Liver injury at various degrees (mild to severe) was found in more than half (59.5%) of the cases. The Spearman correlation analysis suggested a statistically insignificant correlation between liver IL-6 expression and the degree of liver injury (r=0.152; p=0.309). In conclusion, even IL-6 expression was observed in all post-mortem liver specimens, there was an insignificant correlation between IL-6 expression in the liver tissue with the degree of liver injury among fatal COVID-19 patients, suggesting that IL-6 was not the only main factor contributing to liver damage in COVID-19 patients.

The Effects of a Disaster Preparedness app on Community Knowledge and Intentional Behavior in Hurricane Risk Areas.

OBJECTIVE: With the advancement of technology, disaster preparedness related to hurricane hazards can be taught through an app. This study aimed to examine the effect of using an android-based disaster preparedness app on community knowledge and intentional behavior in hurricane risk areas. METHODS: A quasi-experimental study was conducted from October to November, 2020 and a total of 80 respondents were recruited using cluster sampling. The treatment group was given the intervention in the form of the disaster preparedness app for 2 weeks. Meanwhile, the control group received home visits and conventional education about hurricane disasters twice throughout the same period. We then used a Wilcoxon Signed Rank test to analyze the pre-test and post-test and a Mann-Whitney U test to compare between treatment and control groups. RESULTS: After the implementation of the SiBen app, we found a statistically significant difference in knowledge between treatment and control groups (P < 0.003) and intentional behavior between treatment and control groups (P < 0.001). CONCLUSION: The findings indicate that the disaster preparedness app was an effective educational program able to improve the knowledge and intentional behavior among community members in a hurricane risk area.

Interleukin-6 (IL-6) expression of lung tissue in COVID-19 patient severity through core biopsy post mortem.

Introduction: In COVID-19 patients, Interleukin-6 (IL-6) will increase, and the production of antigens will be excessive, which will cause excessive inflammation of the tissues, especially the respiratory tract, which causes fibrosis in the lungs and can lead to death. Objective: To analyze IL-6 expression of lung tissue in COVID-19 patient severity. Methods: The study is an observational analytic design from July to December 2020. COVID-19 patient severity who died was examined for IL-6 expression on lung tissue. The lung tissue sampling uses the core biopsy method. Results: The total number of samples obtained was 38 samples. Characteristics of patients with a mean age of patients were 48 years, male, the most common chief complaint was shortness of breath, mean symptom onset was 5 days, patient length of stay was 10 days, the most common cause of death was a combination of septic shock and ARDS and the most common comorbid diabetes mellitus. There is an increased WBC, neutrophils, platelets, procalcitonin, CRP, BUN, creatinine serum, AST, ALT, and D-dimer. In this study, the average tissue IL-6 expression was 72.63, with the highest frequency of strong positive 47.4%. Conclusion: An increase in IL-6 expression on lung tissue showed the severity of COVID-19 infection.

Serotype Distribution and Antimicrobial Resistance Profile of Haemophilus influenzae Isolated from School Children with Acute Otitis Media.

Haemophilus influenzae is a Gram-negative opportunistic bacterial pathogen of the human respiratory tract. This study describes the prevalence, serotype distribution, and susceptibility profiles of H. influenzae strains isolated from the nasopharynx of school children with acute otitis media (AOM) in Banyumas Regency, Central Java, Indonesia. H. influenzae was isolated from nasopharyngeal swab specimens using chocolate agar plates supplemented with IsoVitaleX and bacitracin. Serotyping was performed using quantitative polymerase chain reaction. Antimicrobial susceptibility profiles were determined using a microdilution broth assay. H. influenzae was present in 69.7% of samples (85/122). Nontypeable H. influenzae (NHTi) was the most common serotype (95.3%), followed by H. influenzae type b (3.5%) and H. influenzae type f (1.2%). All the H. influenzae isolates were susceptible to levofloxacin, ceftriaxone, imipenem, meropenem, cefuroxime, and cefixime. Most isolates were susceptible to sparfloxacin (99%), cefepime (99%), amoxicillin/clavulanic acid 2 : 1 (99%), ampicillin/sulbactam 2 : 1 (96%), chloramphenicol (94%), tetracycline (93%), ampicillin (87%), and clarithromycin (82%). Nineteen percent of the isolates were resistant to cotrimoxazole, and 11% of the isolates were resistant to ampicillin. This study showed that H. influenzae carriage among samples was dominated by NTHi and less susceptible to cotrimoxazole.

Nasopharyngeal carriage rates and serotype distribution of Streptococcus pneumoniae among school children with acute otitis media in Central Java, Indonesia.

Streptococcus pneumoniae is a common bacterial pathogen that causes acute otitis media (AOM) in children. In this study, we investigated nasopharyngeal carriage rates and serotype distributions of S. pneumoniae among school children with AOM in Banyumas Regency, Central Java, Indonesia, from 2018 to 2019. Nasopharyngeal swab specimens and demographic data were collected from 122 children between the ages of 6 and 12. The specimens were cultured for the identification of S. pneumoniae, and serotyping was performed using a sequential multiplex PCR assay. We found that the S. pneumoniae carriage rate was 73 % (89/122) among children with AOM. Serotypes 23A (11 %) and 6A/6B (10 %) were the most common serotypes among the 91 cultured S. pneumoniae strains, followed by 3 (8 %), 14 (7 %), 6C/6D (7 %), 11A/11D (6 %), 15B/15C (4 %) and 35 B (4 %). Moreover, 41 % of the strains could be covered by the 13-valent pneumococcal conjugate vaccine, PCV13. In conclusion, high nasopharyngeal carriage rates of S. pneumoniae were found in school children with AOM, with almost half of the strains being the vaccine-type. This finding provides a baseline for nasopharyngeal carriage of S. pneumoniae in school children with AOM and supports the implementation of pneumococcal conjugate vaccines in Indonesia.

Risk factors for acute otitis media in primary school children: a case-control study in Central Java, Indonesia.

Background: Acute otitis media (AOM) is the most common disease in young children requiring antibiotic treatment. Information on AOM-related determinant risk factors in primary school children is still limited, particularly in Indonesia. This study aims to identify risk factors related to AOM in primary school children in Banyumas Regency, Central Java, Indonesia. Design and Methods: This is an analytical study with a casecontrol design in Banyumas Regency, Indonesia. 3574 children from 6 regions of the Banyumas Regency were recruited for the screening of AOM detection, and confirmation of AOM diagnosis was determined by Otolaryngologist. One hundred and twentyfive cases and 125 control were involved in this study. Data collection was carried out using a structured questionnaire focusing on several variables such as household cooking fuel, house environment, smoking exposure, knowledge of parents, and nutrition status. Univariate, bivariate using chi-square and multivariate with regression logistic was conducted for data analysis. Results: This study highlights the risk of household firewood use (p=0.003), poor nutritional status (p=0.009), and a family history of ear infections (p=0.015) with an increased risk of otitis media. Conclusions: Household firewood use, poor nutritional status and family history of ear infection are factors associated with the occurrence of acute otitis media. It is necessary to provide public health education to prevent exposure to fuel at risk for children and to improve their nutritional status.

Supplementation with Fermented Rice Bran Attenuates Muscle Atrophy in a Diabetic Rat Model.

Fermented rice bran (FRB), a prospective supplement, has been proven to ameliorate certain medical conditions. However, its nutraceutical effect on muscle atrophy has never been investigated. The present study aimed to evaluate the effect of FRB on muscle atrophy in a streptozotocin (STZ)-induced diabetic rat model. Three groups of Sprague-Dawley rats, namely the control, STZ, and FRB groups, were treated as follows. The diabetic groups (STZ and FRB) were injected intraperitoneally with STZ (40 mg/kg BW), whereas the control group was injected with the vehicle. The STZ and control groups were fed the AIN93M diet, and the FRB group was fed 10% of FRB based on the AIN93M diet. The diabetic groups had reduced muscle size compared to the control group; however, these changes were alleviated in the FRB group. Moreover, the FRB group had a significantly lower expression of FBXO32/Atrogin-1 and TRIM63/MuRF1 (p < 0.05) due to blocked NF-κB activation. In conclusion, the anti-inflammatory effect of FRB may be beneficial for ameliorating muscle atrophy in diabetic conditions.