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Sri Lanka has a rapidly aging population in South Asia, but little attention is given to financial preparedness for retirement. This study expects to provide an overview of the current retirement system in Sri Lanka and investigate financial and pension literacy's role in retirement preparedness. This study administered an online survey to study retirement preparedness subjectively (n = 142) and objectively (n = 115) among the EPF contributors. This non-experimental study uses an online survey to assess financial and pension literacy's roles in retirement preparedness. This study used ordered logistic (Ologit) regressions and ordinary least squares (OLS) regressions to test the two hypotheses. Results indicate a positive and statistically significant association between financial (only objective measure) and pension literacy and retirement preparedness. However, another study shows no synergy effect between financial and pension literacy. Conclusively, drawing policymakers' attention to diversifying EPF investments, including financial and pension literacy concepts in workplace workshops and studying pension literacy and retirement preparedness in different samples.

Abstract Background To evaluate the associations between glycated hemoglobin (HbA1c) at admission and 6-month mortality and outcomes after out-of-hospital cardiac arrest (OHCA) treated by hypothermic targeted temperature management (TTM). Methods This single-center retrospective cohort study included adult OHCA survivors who underwent hypothermic TTM from December 2011 to December 2019. High HbA1c at admission was defined as a level higher than 6%. Poor neurological outcomes were defined as cerebral performance category scores of 3–5. The primary outcome was 6-month mortality. The secondary outcome was the 6-month neurological outcome. Descriptive statistics, log-rank tests, and multivariable regression modeling were used for data analysis. Results Of the 302 patients included in the final analysis, 102 patients (33.8%) had HbA1c levels higher than 6%. The high HbA1c group had significantly worse 6-month survival (12.7% vs. 37.5%, p 6% than in those with HbA1c ≤6%. In the multivariable logistic regression analysis, HbA1c > 6% was independently associated with 6-month mortality (OR 5.85, 95% CI 2.26–15.12, p

Protein methyl transferases play critical roles in numerous regulatory pathways that underlie cancer development, progression and therapy-response. Here we discuss the function of PRMT5, a member of the nine-member PRMT family, in controlling oncogenic processes including tumor intrinsic, as well as extrinsic microenvironmental signaling pathways. We discuss PRMT5 effect on histone methylation and methylation of regulatory proteins including those involved in RNA splicing, cell cycle, cell death and metabolic signaling. In all, we highlight the importance of PRMT5 regulation and function in cancer, which provide the foundation for therapeutic modalities targeting PRMT5.

Abstract Background Less is known about the impact of cancer on household assets and household financial portfolio during which cancer survivors face higher mortality risk. Economic theory predicts that cancer survivors would deplete their wealth in such a way that meets immediate financial needs for treatment and that hedges the risk of anticipated medical expenses associated with recurrence. Building upon this prediction, we examine long-term changes in household assets in response to cancer diagnosis among middle-aged and elderly Americans (age ≥ 50). Results Using the 2000–2014 waves of the Health and Retirement Study, we estimated the household fixed effects regression that regresses household assets on time elapsed since cancer diagnosis (≤ 2 years, > 2 but ≤4 years, > 4 but ≤6 years, and > 6 but ≤8 years). Regression estimates were adjusted for demographic characteristics, general health condition, employment outcomes, and household economic attributes. Household assets were measured by total net worth as well as the amount of savings held in each asset category. The loss of household assets attributable to cancer was estimated to be $125,832 in 2015 dollars per household with a cancer patient. This change came from statistically significant reductions in investment assets, miscellaneous savings, real estate equity, and business equity, and increases in unsecured debt. We also found 17.2–28.0% increases in cash and cash-equivalent assets from + 2 years since diagnosis through the rest of the study periods. The accumulation of cash was observed for both the well-insured group (multiple coverages) and those with limited insurance (single coverage). Conclusions The results showed evidence of both asset depletion and precautionary accumulation of liquid assets among cancer survivors, which reduces risk exposure of household financial portfolio. Our findings highlighted that household asset is an important source of liquidity to finance cancer care and to absorb the expected expenditure risk associated with cancer recurrence. We also showed that health insurance provides limited coverage of health risks associated with cancer.

While Rwanda is aiming at environmental pollution resilience and green growth, some industries are still discharging untreated effluent into the environment. This study gives a general overview of the compliance level of industrial effluent discharge in Rwanda and the linked negative environmental impacts. It comprises qualitative and quantitative analyses of data obtained from wastewater samples collected from five selected industries in Rwanda. The selected industries had previously been audited and monitored by the Rwanda Environment Management Authority (REMA), due to complains from neighboring residents. The study found that the effluent discharge from wastewater treatment plants (WWTP) for all concerned industries failed to comply with (i) oil and grease (O&G) national and international tolerable parameter limits or the (ii) fecal coliforms national standard. In addition, a compliance level of 66.7% was observed for key water quality monitoring parameters (pH, dissolved oxygen (DO), biochemical oxygen demand (BOD), chemical oxygen demand (COD), total suspended solids (TSS), and heavy metals (i.e., lead (Pb), cadmium (Cd), and chromium (Cr)). Following these study findings, one industry was closed by the REMA for deliberately discharging untreated effluent into an adjacent river. This study recommends the adoption of the best available technology for effluent treatment, installation or renovation of existing WWTPs, and the relocation to industrial zones of industries adjacent to fragile environments.

RNF5 is a ubiquitin ligase regulating ER stress response. Here the authors show that Rnf5 deficiency potentiates immune response against melanoma via altered microbiota, and isolate bacterial strains that confer the same phenotype to wild type mice.

Abstract Background The PI3K/Akt and the STAT3 pathways are functionally associated in many tumor types. Both in vitro and in vivo studies have revealed that either biochemical or genetic manipulation of the STAT3 pathway activity induce changes in the same direction in Akt activity. However, the implicated mechanism has been poorly characterized. Our goal was to characterize the precise mechanism linking STAT3 with the activity of Akt and other AGC kinases in cancer using melanoma cells as a model. Results We show that active STAT3 is constitutively bound to the PDK1 promoter and positively regulate PDK1 transcription through two STAT3 responsive elements. Transduction of WM9 and UACC903 melanoma cells with STAT3-small hairpin RNA decreased both PDK1 mRNA and protein levels. STAT3 knockdown also induced a decrease of the phosphorylation of AGC kinases Akt, PKC, and SGK. The inhibitory effect of STAT3 silencing on Akt phosphorylation was restored by HA-PDK1. Along this line, HA-PDK1 expression significantly blocked the cell death induced by dacarbazine plus STAT3 knockdown. This effect might be mediated by Bcl2 proteins since HA-PDK1 rescued Bcl2, Bcl-XL, and Mcl1 levels that were down-regulated upon STAT3 silencing. Conclusions We show that PDK1 is a transcriptional target of STAT3, linking STAT3 pathway with AGC kinases activity in melanoma. These data provide further rationale for the ongoing effort to therapeutically target STAT3 and PDK1 in melanoma and, possibly, other malignancies.

Fouling mechanisms associated with membrane-based polysaccharide enrichment were determined using a dense ultrafiltration (UF) membrane. Dextran with different molecular weights (MWs) was used as a surrogate for polysaccharides. The influence of dextran MW on fouling mechanisms was quantified using the Hermia model. Flux data obtained with different dextran MWs and filtration cycles were plotted to quantify the more appropriate fouling mechanisms among complete pore blocking, standard pore blocking, intermediate pore blocking, and cake filtration. For 100,000 Da dextran, all four mechanisms contributed to the initial fouling. As the filtration progressed, the dominant fouling mechanism appeared to be cake filtration with a regression coefficient (R2) of approximately 0.9519. For 10,000 Da, the R2 value for cake filtration was about 0.8767 in the initial filtration. Then, the R2 value gradually decreased as the filtration progressed. For 6000 Da, the R2 values of the four mechanisms were very low in the initial filtration. However, as the filtration progressed, the R2 value for cake filtration reached 0.9057. These results clearly show that the fouling mechanism of dense UF membranes during polysaccharide enrichment can be quantified. In addition, it was confirmed that the dominant fouling mechanism can change with the size of the polysaccharide and the duration of filtration.

The optimal operating conditions of a combined dissolved air flotation (DAF)-microfiltration (MF) process to respond to changes in raw water quality were investigated by operating a pilot plant for two years. Without DAF pre-treatment (i.e., MF alone), MF operated stably with a transmembrane pressure (TMP) increase of 0.24 kPa/d when the turbidity of raw water was low and stable (max. 13.4 NTU). However, as the raw water quality deteriorated (max. 76.9 NTU), the rate of TMP increase reached 43.5 kPa/d. When DAF pre-treatment was applied (i.e., the combined DAF-MF process), the MF process operated somewhat stably; however, the rate of TMP increase was relatively high (i.e., 0.64 kPa/d). Residual coagulants and small flocs were not efficiently separated by the DAF process, exacerbating membrane fouling. Based on the particle count analysis of the DAF effluent, the DAF process was optimised based on the coagulant dose and hydraulic loading rate. After optimisation, the rate of TMP increase for the MF process stabilised at 0.17 kPa/d. This study demonstrates that the combined DAF-MF process responded well to substantial changes in raw water quality. In addition, it was suggested that the DAF process must be optimised to avoid excessive membrane fouling.

Nitrosamines can be produced during the manufacture of rubber-type products such as pacifiers or the nipples of baby bottles. Humans can be exposed to the nitrosamines in these products when they are eluted into saliva. In this study, we compared the efficiency of electron impact ionization (EI), atmospheric pressure chemical ionization (APCI), and electrospray ionization (ESI) methods for the analysis of nine nitrosamines eluted into artificial saliva. In addition, nine nitrosamines eluted from 54 rubber-type products (rubber, thermoplastic elastomer, thermoplastic polyurethane, and polyurethane) marketed in Korea were monitored. Finally, non-carcinogenic and carcinogenic risk assessments of oral exposure to nine nitrosamines were performed based on the monitoring results. EI-GC-MS/MS performed the best for the simultaneous analysis of these nine nitrosamines with respect to overall linearity, trace analysis limit of detection (less than 1 μg), recovery (average 108.66 ± 9.32%), and precision (less than 6%), compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS) (APCI and ESI) methods. Using the EI-GC-MS/MS method, these nine nitrosamines eluted into artificial saliva from 54 rubber-type products were monitored. Based on the monitoring data, risk assessment was performed by calculating the margin of exposure (MOE) for the respective nitrosamines detected. As a result, these nitrosamines were confirmed to be safe with regard to both non-carcinogenic and carcinogenic risks.

Melanoma is one of the most lethal cutaneous malignancies, characterized by chemoresistance and a striking propensity to metastasize. The transcription factor ATF2 elicits oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, we show that expression of a transcriptionally inactive form of Atf2 (Atf2Δ8,9) promotes development of melanoma in mouse models. Atf2Δ8,9-driven tumors show enhanced pigmentation, immune infiltration, and metastatic propensity. Similar to mouse Atf2Δ8,9, we have identified a transcriptionally inactive human ATF2 splice variant 5 (ATF2SV5) that enhances the growth and migration capacity of cultured melanoma cells and immortalized melanocytes. ATF2SV5 expression is elevated in human melanoma specimens and is associated with poor prognosis. These findings point to an oncogenic function for ATF2 in melanoma development that appears to be independent of its transcriptional activity.

In this work, liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated for screening and confirmation of 64 illicit compounds in dietary supplements. The target compounds were illegally used pharmaceutical drugs, prohibited compounds, and not authorized ingredients for different therapeutics (sexual enhancement, weight loss, muscular strengthening, and relaxing products). The validation procedure was performed to evaluate selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, and precision according to the Association of Official Analytical Chemists guidelines. The linearity was >0.98 in the range of 0.5–200 µg L−1. The LOQs were in the range 1–10 µg kg−1 for all target compounds. The accuracy (expressed as recovery) was 78.5–114%. The precision (expressed as the relative standard deviation) was below 9.15%. The developed method was applied for the determination of illicit compounds in dietary supplements collected from websites. As a result, the total detection rate was 13.5% (27 samples detected in 200 samples). The concentrations of detected samples ranged from 0.51 to 226 mg g−1. The proposed methodology is suitable for monitoring the adulteration of illicit compounds in dietary supplements.

Despite the remarkable clinical response of melanoma harboring BRAF mutations to BRAF inhibitors (BRAFi), most tumors become resistant. Here, we identified the downregulation of the ubiquitin ligase RNF125 in BRAFi-resistant melanomas and demonstrated its role in intrinsic and adaptive resistance to BRAFi in cultures as well as its association with resistance in tumor specimens. Sox10/MITF expression correlated with and contributed to RNF125 transcription. Reduced RNF125 was associated with elevated expression of receptor tyrosine kinases (RTKs), including EGFR. Notably, RNF125 altered RTK expression through JAK1, which we identified as an RNF125 substrate. RNF125 bound to and ubiquitinated JAK1, prompting its degradation and suppressing RTK expression. Inhibition of JAK1 and EGFR signaling overcame BRAFi resistance in melanoma with reduced RNF125 expression, as shown in culture and in in vivo xenografts. Our findings suggest that combination therapies targeting both JAK1 and EGFR could be effective against BRAFi-resistant tumors with de novo low RNF125 expression.

The endoplasmic reticulum (ER) responds to changes in intracellular homeostasis through activation of the unfolded protein response (UPR). Yet, it is not known how UPR-signaling coordinates adaptation versus cell death. Previous studies suggested that signaling through PERK/ATF4 is required for cell death. We show that high levels of ER stress (i.e., ischemia-like conditions) induce transcription of the ubiquitin ligases Siah1/2 through the UPR transducers PERK/ATF4 and IRE1/sXBP1. In turn, Siah1/2 attenuates proline hydroxylation of ATF4, resulting in its stabilization, thereby augmenting ER stress output. Conversely, ATF4 activation is reduced upon Siah1/2 KD in cultured cells, which attenuates ER stress-induced cell death. Notably, Siah1a(+/-)::Siah2(-/-) mice subjected to neuronal ischemia exhibited smaller infarct volume and were protected from ischemia-induced death, compared with the wild type (WT) mice. In all, Siah1/2 constitutes an obligatory fine-tuning mechanism that predisposes cells to death under severe ER stress conditions.

The article focuses on the tumor-intrinsic function of the orphan nuclear receptor NR2F6 in regulating antitumor immunity. It study identifies NR2F6 as an important factor in melanoma with potential implications for immunotherapy response. It mentions Genetic ablation of NR2F6 improves the response to PD-1 therapy, and loss of NR2F6 leads to increased abundance of effector CD8+ T cells, attenuated tumor development, and decreased tumor growth.

Arginyl-tRNA-protein transferase 1 (ATE1) catalyses N-terminal protein arginylation, a post-translational modification implicated in cell migration, invasion and the cellular stress response. Herein, we report that ATE1 is overexpressed in NRAS-mutant melanomas, while it is downregulated in BRAF-mutant melanomas. ATE1 expression was higher in metastatic tumours, compared with primary tumours. Consistent with these findings, ATE1 depletion reduced melanoma cell viability, migration and colony formation. Reduced ATE1 expression also affected cell responses to mTOR and MEK inhibitors and to serum deprivation. Among putative ATE1 substrates is the tumour suppressor AXIN1, pointing to the possibility that ATE1 may fine-tune AXIN1 function in melanoma. Our findings highlight an unexpected role for ATE1 in melanoma cell aggressiveness and suggest that ATE1 constitutes a potential new therapeutic target. [ABSTRACT FROM AUTHOR]