Clinical Utility of Genetic Variants in PNPLA3 and TM6SF2 to Predict Liver-Related Events in Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND AND AIMS: Fibrosis-4 (FIB-4) index and genetic polymorphisms have been used in assessing the risk of liver-related events (LRE) in metabolic dysfunction-associated steatotic liver disease (MASLD). To establish a more efficient prediction strategy for LRE, we investigated a combined approach that uses the FIB-4 index and genetic polymorphisms. METHODS: We enrolled 1304 Japanese patients with biopsy-proven MASLD in this longitudinal multicenter cohort study. PNPLA3, TM6SF2, GCKR and MBOAT7 genotypes were genotyped, and polygenic risk score high fat content (PRS-HFC) were calculated. RESULTS: During the follow-up period of 8.1 year, 96 LRE occurred and 53 patients died. PNPLA3, TM6SF2 and GCKR genotypes were associated with LRE development. We divided patients into three groups based on the FIB-4 index and PNPLA3 and TM6SF2 genotype. The cumulative LRE development rate in each group was 2.1%/28.9%/53.5%, respectively, at 10 years. Multivariate analysis revealed hazard ratios (HRs) for LRE of 10.72 in the high-risk group and 4.80 in the intermediate-risk group. Overall survival in each group was 98.8%/85.2%/72.4%, respectively, at 10 years. HRs for prognosis were 8.74 in the high-risk group and 5.62 in the intermediate-risk group. Patients with FIB-4 index > 2.67 and high PRS-HFC had HR of 6.70 for LRE development and HR of 6.07 for prognosis compared to patients with FIB-4 ≤ 2.67. CONCLUSIONS: The approach of measuring the FIB-4 index first followed by assessment of genetic polymorphisms efficiently detected patients at high risk of developing LRE. Therefore, this two-step strategy could be used as a screening method in large populations of patients with MASLD.

Utilizing Bladder Diaries to Prevent Unnecessary Treatment in Patients With Storage Dysfunction: A Retrospective Study.

Introduction A frequency volume chart (FVC) or bladder diary (BD) is used to diagnose lower urinary tract symptoms and to determine the effectiveness of treatment. In outpatient practice, patients who use an FVC or BD may experience improvement in storage symptoms and not desire further treatment. The aim of this study was to determine the characteristics of patients who did not desire treatment after BD recording and to assess the changes in storage symptoms after BD recording. Methods This was a retrospective study. Patients who completed a three-day BD record were included. The patients were divided into two groups: those whose symptoms improved after using a BD and no longer desired treatment, and those who desired treatment. We compared endpoints including patient background, BD, Overactive Bladder Symptom Score (OABSS), and International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) score. Results We recruited 79 patients. Four patients were excluded (two were minors and two due to cognitive impairment). Thus, 75 patients were included in the analysis. Of these, 27 (36.0%) did not desire treatment for storage symptoms after BD recording. Compared with the group of patients who desired treatment, those who did not desire treatment had significantly lower daytime and nighttime frequency and number of leaks recorded in their BD, and there were fewer patients with nocturia and habitual caffeine consumption. Baseline OABSS and ICIQ-UI SF scores were lower and there were no significant changes in storage symptoms after BD recording. The cut-off value for the baseline total score of OABSS that did not desire treatment for storage symptoms after BD recording was 6 points. Conclusion In this study, 36.0% of patients no longer desired treatment for storage symptoms after using a BD. These patients initially exhibited a normal daily urinary frequency and mild storage symptoms. These findings suggest that among patients presenting to the outpatient clinic with storage symptoms, those with mild symptom severity and a total OABSS of 6 points or less may be able to avoid unnecessary treatment through BD recording.

Quantitative relationship between grip strength and quality of life in the older adult based on a restricted cubic spline model.

Background: Grip strength have been showed diverse associations with quality of life for the older adult population in the literature, still there is lack of evidence of the threshold value of grip strength for maintaining good quality of life in older adults. The purpose of this study was to study the dose-effect relationship between grip strength and quality of life in the older adult, and to explore the factors affecting quality of life in the older adult, so as to provide effective theoretical basis for realizing healthy aging. Methods: A total of 105 older adult people over 60 years old were selected from 3 communities in Beijing. Grip strength was measured by hand dynamometer apparatus and quality of life was assessed by 36-item Short-Form (SF-36). On the basis of controlling confounding factors, the dose-effect relationship between grip strength and quality of life was analyzed with the restricted cubic spline model. Results: The results showed that there was a dose-effect relationship between grip strength and physical component summary (PCS) (p < 0.01). However, grip strength was not significantly associated with mental component summary (MCS) (p > 0.05). The threshold value of grip strength for male and female is 34.75 and 23.2 kg, for normal weight group and overweight and obesity group is 24.82 and 29.00 kg, for 60-69, 70-79, 80+ years group is 24.88, 23.37, and 22.97 kg, respectively. When the grip strength value is lower than the threshold value, the increase of grip strength was related to significant improvement of quality of life of the older adult, and when the grip strength value is higher than the threshold value, the quality of life can be maintained in good condition. Conclusion: A dose-effect relationship was found between grip strength and physical health in quality of life. Results of our study indicated that the grip strength of the older adults needed to be greater than certain threshold values to maintain good quality of life.

Chemometrics and analytical blank on the at-line monitoring of Zika-VLP production using near-infrared spectroscopy.

The Zika disease caused by the Zika virus was declared a Public Health Emergency by the World Health Union (WHO), with microcephaly as the most critical consequence. Aiming to reduce the spread of the virus, biopharmaceutical organizations invest in vaccine research and production, based on multiple platforms. A crescent vaccine production approach is based on virus-like particles (VLP), for not having genetic material in its composition, hypoallergenic and non-mutant character. For bioprocess, it is essential to have means of real-time monitoring, which can be assessed using process analysis techniques such as Near-infrared (NIR) spectroscopy, that can be combined with chemometric methods, like Partial-Least Squares (PLS) and Artificial Neural Networks (ANN) for prediction of biochemical variables. This work proposes a biochemical Zika VLP upstream production at-line monitoring model using NIR spectroscopy comparing sampling conditions (with or without cells), analytical blank (air, ultrapure water), and spectra pre-processing approaches. Seven experiments in a benchtop bioreactor using recombinant baculovirus/Sf9 insect cell platform in serum-free medium were performed to obtain biochemical and spectral data for chemometrics modeling (PLS and ANN), composed by a random data split (80 % calibration, 20 % validation) for cross-validation of the PLS models and 70 % training, 15 % testing, 15 % validation for ANN. The best models generated in the present work presented an average absolute error of 1.59 × 105 cell/mL for density of viable cells, 2.37 % for cell viability, 0.25 g/L for glucose, 0.007 g/L for lactate, 0.138 g/L for glutamine, 0.18 g/L for glutamate, 0,003 g/L for ammonium, and 0.014 g/L for potassium.

Analysis of the quality of life of tuberculosis patients based on the SF-36 form (case study in Banyumas Regency).

INTRODUCTION: Indonesia is one of the countries with the largest TB burden. To date, the success of TB treatment has only been seen from microscopic examination but has not really taken into account the quality of life of TB patients. Decreased quality of life in TB patients can cause delays in treatment and have a negative impact on the continuity of treatment, causing treatment to be interrupted or incomplete (drop out). This research was conducted with the aim of knowing the quality of life of TB patients during the treatment period along with the factors that influence it. METHODS: Measuring quality of life in this study used the SF-36 instrument. This study was analytical research with a cross-sectional study design. Study subjects were all TB patients who were still undergoing TB treatment. This study was conducted in September-November 2020. Independents variables were gender, education, marital status, occupation status, income, comorbidity, smoking habits, anxiety level, emotional support, and material support. Dependent variable was quality of life of TB patients. The data analysis used was univariate and bivariate (chi square test). RESULTS: The majority of TB patients had a poor quality of life (51,2%). Mental health was the highest domain with a score of 88.48, while physical role was the lowest domain with a score of 40.24. The factor that significantly influenced the quality of life of TB patients was emotional support from their families (p value 0.039). CONCLUSION: More TB patients had a poor quality of life with physical health was the lowest domain. Emotional support from the families of TB patients was the main factor causing the TB patient's quality of life to be low. It is important for health service providers to promote health and provide assistance to families of TB patients in an effort to increase emotional support for TB patients. Thus, TB patients can undergo treatment well and their quality of life improves during treatment.

The relationship between static and dynamic postural deformities with pain and quality of life in non-athletic women.

BACKGROUND: The assessment of the postural condition with functional tests are used with the least facilities in the shortest time, for a wide the range of movements for different parts of the body. Both static and dynamic posture measurements are predictive of injury. These two assessments provide different information regarding posture control. Also, with the advancement of this technology, the speed of posture assessment and deformity diagnosis can be increased and done with the minimum facilities. This can signal a new method for the quick diagnosis of abnormalities and ultimately prevent or correct psychological effects and musculoskeletal pain in the future. Because as seen according to the citations, abnormalities cause musculoskeletal pains, movement restrictions and ultimately affect the quality of life. METHODS: The current research is of the applied and semi-experimental type, and in terms of the results it is of the relational and correlational type. In this research, 148 non-Athletic women from Fardis City participated, in which the results obtained from the static evaluation was analyzed by the Posture Screen application after taking photos from four directions using a smartphone, and also the dynamic evaluation was identified and analyzed by the researcher using the overhead squat test of compensatory movements, with the data that from Cornell pain and quality of life SF-36 questionnaires was. Data description and correlation between variables were done with the η coefficient method. RESULTS: According to the findings there is a positive and significant correlation between the prevalence of uneven pelvic deformity and the amount of pain in non-athletic women (P = 0.036, η (148) = 0.17). In other words, pain increased significantly when the pelvis was changed from a normal position to a lateral deviation position. Also, there is a negative and significant relationship between the prevalence of deformity of knee movement, back arch, straight back, heel lift and the quality of life in non-athletic women (P = 0.020, η (148) = 0.19). CONCLUSIONS: According to the results, deformities have an effect on pain and the frequency of pain, on the other hand, in the present study, dynamic evaluations showed deformities more accurately than static evaluations.

Quality assessment of common anti-malarial medicines marketed in Gambella, National Regional State, South Western-Ethiopia.

BACKGROUND: Over the past years, there has been a growing concern that a considerable amount of anti-malarial supply in the underdeveloped world particularly in the private sector, is of poor quality. The World Health Organization (WHO) has received about 1500 reports that mentions instances of substandard and falsified products since 2013. The majority of the reports concerned antibiotics and anti-malarials. The majority of reports (42%) originate from the WHO African region. OBJECTIVE: This study intends to assess the quality of the most widely used anti-malarial medications [artemether-lumefantrine tablets, chloroquine phosphate tablets, primaquine phosphate tablets, artesunate, and artemether injections] in Gambella, South-West, Ethiopia. METHODS: A total of 52 samples were collected on June 2022 from Gambella National Regional State, Ethiopia. Half of the districts (six) located in the four zones of the region were chosen using simple random sampling technique. All drug retail outlets available in the selected districts (locally known as woredas) were included. The samples were subjected to visual inspection with a tool adopted from the joint WHO/FIP/ USP checklist. The pharmacopeial tests for identification, uniformity of dosage forms, assay, thickness, diameter, hardness, friability, disintegration test, dissolution, and sterility tests were carried out according to the USP 44-NF 39 and International Pharmacopoeia 11th edition, 2022 monographs. RESULTS AND DISCUSSION: Only 25% of the samples were registered on the Ethiopian Food and Drug Authority (EFDA's) electronic regulatory/ registration system (ERIS). Besides, 88.8% of artemether injection products were presented in clear glass ampoules. This might expose the products to photochemical degradation that leads to in loss of anti-plasmodial activity. In addition, 50% of the artemether products assessed were not bioequivalent with the comparator product in the in vitro dissolution comparison tests. Overall, the study findings reveal a high prevalence (58.3%) of substandard anti-malarial drugs in the region. The stated percent of the samples had failed in one or more of the quality test parameters assessed in this study. CONCLUSION: The study findings reveal a high prevalence (58.3%) of substandard anti-malarial drugs in the region. Only a quarter were registered and 38% of the unregistered products failed the quality tests. Hence, the national, regional medicine regulatory bodies and other stake holders should perform the required roles to circumvent presence of Substandard and Falsified (SF) anti-malarial drugs in the study sites.

Analyzing the role of TM4SF1 expression in pancreatic adenocarcinoma: understanding prognostic implications and therapeutic opportunities.

Background: Pancreatic adenocarcinoma (PAAD) is a highly lethal malignancy characterized by aggressive growth and poor prognosis. Understanding the molecular mechanisms underlying PAAD is crucial for developing effective therapies. This study aimed to explore the role of TM4SF1 and other key genes in PAAD progression, their prognostic implications, and therapeutic opportunities. Methods: Differential gene expression analysis was performed using PAAD and normal tissue samples to identify upregulated genes, with TM4SF1 emerging as significantly elevated in PAAD. Functional enrichment analysis elucidated associated signaling pathways. A prognostic model comprising BPIFB4, PLEKHN1, CPTP, DVL1, and DDR1 was developed using least absolute shrinkage and selection operator (LASSO) regression and validated in an independent cohort. Genetic mutation analysis provided insights into the functional significance of identified genes. Pharmacogenomic analysis examined associations between gene expression and drug sensitivity. Experimental validation included quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses to confirm gene expression patterns and protein levels. Results: Lower TM4SF1 expression correlated with enhanced anti-tumor immune activity in PAAD, suggesting a complex interplay between genetic expression and immune response. The prognostic model showed robust associations with patient survival outcomes, validated across diverse patient cohorts. Genetic mutation analysis highlighted potential therapeutic targets. Pharmacogenomic analysis revealed correlations between gene expression profiles and drug responsiveness, suggesting personalized treatment strategies. Experimental validation confirmed elevated TM4SF1 levels in tumor tissues and demonstrated its role in promoting cancer cell proliferation and colony formation. Conclusions: This study advances understanding of the molecular landscape of PAAD, emphasizing TM4SF1 as a key regulator and potential therapeutic target. The integration of genetic expression, immune response dynamics, and pharmacogenomics offers a multifaceted approach to personalized treatment strategies for PAAD, paving the way for improved patient outcomes and novel therapeutic interventions. Further research is warranted to elucidate the clinical utility of targeting TM4SF1 and other identified genes in PAAD management.

Prognostic impact of DTA mutation and co-occurring mutations in patients with myelodysplastic syndrome.

OBJECTIVE: To evaluate the frequency and prognostic significance of DTA (DNMT3A、TET2、ASXL1) gene mutation and co-occurring mutations in patients with myelodysplastic syndrome (MDS). METHODS: The clinical data of 102 newly diagnosed MDS patients who accepted Next Generation Sequencing (NGS) was retrospectively analyzed. According to whether the patients had DTA gene mutation, the patients were divided into DTA mutated (DTA-mut) group and wild type (DTA-wt) group, and the relationship between gene mutation and clinical characteristics and prognosis was analyzed. RESULTS: Among the 102 MDS patients, 96% (98/102) presented with mutation, while the mean number of mutations was 3.04 mutations/patient. DTA-mut was detected in 56.9% (58/102) patients. The most frequent co-mutated genes in DTA-mut group were SF3B1 (25.8%), RUNX1 (24.1%), U2AF1 (18.9%), SRSF2, EZH2, SETBP1 (17.2%), STAG2 (15.5%), IDH2 (12.1%) and BCOR, CBL (10.3%). The two groups showed no significant differences in ages, blood parameters, bone marrow blasts, WHO 2022 classification, IPSS-R risk category and rate of conversion to leukemia. Compared with the DTA-wt group, the mutation frequency of RUNX1 was higher (P = 0.02), while mutation frequency of TP53 was lower (P = 0.001) and the mutation frequency of ≥ 3 co-mutated genes was higher in DTA-mut group (P = 0.00). Survival analysis showed that the overall survivals (OS) of DTA-mut patients was significantly inferior to that of DTA-wt patients (P = 0.0332). According to IPSS-R classification, a statistically significant difference in OS was only observed in higher risk (IPSS-R > 3.5) group (P = 0.0058). In the context of DTA mutation, the OS of patients with RUNX1 mutation was shorter than that of patients without RUNX1 mutation significantly (P = 0.0074). The OS of patients with SF3B1 mutation was longer than that of patients without SF3B1 mutation, but there was no statistical difference (P = 0.0827). DTA mutations were not independent prognostic factors when DTA and co-mutated genes with frequency > 10% were considered in Cox regression model (P = 0.329). However, multivariate analysis confirmed an independently adverse prognosis of RUNX1 co-mutation (P = 0.042, HR = 2.426, 95% CI:1.031-5.711) in DTA-mut cohort. Moreover, our multivariable analysis suggests that SRSF2-mut was an independent poor prognostic factor for all MDS patients (P = 0.047), but lost significance (P = 0.103) for DTA-mut patients. CONCLUSIONS: DTA mutations are frequently observed in patients with MDS, often accompanied by genes involved in RNA splicing and transcription factors like SF3B1 and RUNX1. DTA and concomitant mutations affect prognosis in MDS patients and RUNX1 was identified as an independent poor prognostic factor in patients with DTA mutations.

Yoga and nutritional therapies for promoting health-related quality of life in persons with metabolic syndrome-An interventional observational study.

Introduction: A group of related risk factors known as central obesity, elevated blood pressure, impaired fasting glucose, elevated triglycerides (TGs), and low levels of high-density lipoprotein (HDL) are collectively referred to as metabolic syndrome (MetS). A low quality of life (QoL) in terms of health is linked to MetS. This study sought to determine how lifestyle modifications affected the health-related quality of life (HRQoL) of primary care patients with MetS. Materials and Methods: In this study, we randomized 300 subjects diagnosed with MetS as per the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, into control, yoga, and yoga + diet groups according to their intervention which was given for 6 months. Socio-demographic, anthropometric, and physiological and biochemical parameters were collected at baseline, 3 months, and 6 months. The 36-Item Short Form Health Survey (SF-36) was also used to assess HRQoL. Results: The results of this study indicate that yoga + diet and yoga intervention led to significant decrease in metabolic risk factors, such as waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), TGs, and increase in HDL at 3 months and 6 months from baseline. SF-36 score also showed increment (from 0 score to 100) at 3 months and 6 months, which indicates improvement in HRQoL. Conclusion: Dietary changes and yoga are useful strategies for reducing the risk of MetS, which improves QoL in relation to health. Incorporating yoga practices and advocating a balanced diet within primary care systems can significantly benefit individuals with or at risk of MetS.

An exploration into self-reported inactivity behaviours of adults with an intellectual disability using physical activity questionnaires.

BACKGROUND: Inactivity is a correlate of adverse health. Adults with an intellectual disability (ID) are more inactive than the general population and often present with more complex health issues. Self-reported activity questionnaires such as the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and Rapid Assessment of Physical Activity (RAPA) questionnaire are the predominant source of activity information because of their low cost, non-invasive nature, ease of administration and interpretation of results. METHODS: Correlates of inactivity among the general and ID populations were identified through a literature scoping review. Inactivity was measured using the RAPA and the IPAQ-SF. A multiple-imputation chained equation was used to impute missing data. Using Pearson chi-squared analyses, relationships between these correlates as well as covariates of age, sex, level of ID, body mass index (BMI) and aetiology, and RAPA and IPAQ-SF categories were explored. Logistic regression provided more detailed analyses. Results were summarised using the Systems of Sedentary Behaviour framework. Spearman correlations examined the IPAQ-SF and RAPA relationships. RESULTS: Three correlates for inactivity emerged from the IPAQ-SF and RAPA questionnaire. Up after 07:00 h was a correlate for both. Difficulty walking 100 yards and epilepsy were additional correlates of inactivity. Weak but significant correlations were seen between IPAQ-SF and RAPA scores. CONCLUSIONS: High inactivity levels are present in adults with an ID. The IPAQ-SF and RAPA questionnaires are weakly correlated.

Team players in the pathogenesis of metabolic dysfunctions-associated steatotic liver disease: The basis of development of pharmacotherapy.

Nutrient metabolism is regulated by several factors. Social determinants of health with or without genetics are the primary regulator of metabolism, and an unhealthy lifestyle affects all modulators and mediators, leading to the adaptation and finally to the exhaustion of cellular functions. Hepatic steatosis is defined by presence of fat in more than 5% of hepatocytes. In hepatocytes, fat is stored as triglycerides in lipid droplet. Hepatic steatosis results from a combination of multiple intracellular processes. In a healthy individual nutrient metabolism is regulated at several steps. It ranges from the selection of nutrients in a grocery store to the last step of consumption of ATP as an energy or as a building block of a cell as structural component. Several hormones, peptides, and genes have been described that participate in nutrient metabolism. Several enzymes participate in each nutrient metabolism as described above from ingestion to generation of ATP. As of now several publications have revealed very intricate regulation of nutrient metabolism, where most of the regulatory factors are tied to each other bidirectionally, making it difficult to comprehend chronological sequence of events. Insulin hormone is the primary regulator of all nutrients' metabolism both in prandial and fasting states. Insulin exerts its effects directly and indirectly on enzymes involved in the three main cellular function processes; metabolic, inflammation and repair, and cell growth and regeneration. Final regulators that control the enzymatic functions through stimulation or suppression of a cell are nuclear receptors in especially farnesoid X receptor and peroxisome proliferator-activated receptor/RXR ligands, adiponectin, leptin, and adiponutrin. Insulin hormone has direct effect on these final modulators. Whereas blood glucose level, serum lipids, incretin hormones, bile acids in conjunction with microbiota are intermediary modulators which are controlled by lifestyle. The purpose of this review is to overview the key players in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) that help us understand the disease natural course, risk stratification, role of lifestyle and pharmacotherapy in each individual patient with MASLD to achieve personalized care and target the practice of precision medicine. PubMed and Google Scholar databases were used to identify publication related to metabolism of carbohydrate and fat in states of health and disease states; MASLD, cardiovascular disease and cancer. More than 1000 publications including original research and review papers were reviewed.

The Association Between Sleep and Quality of Life Among Visitors of Lifestyle Clinics at the Ministry of National Guard-Health Affairs, Western Region, Saudi Arabia.

BACKGROUND: Sleep quality significantly impacts health-related quality of life (QoL). However, the link between sleep quality and QoL needs further exploration, especially in the context of Saudi Arabia. OBJECTIVE: To assess the effect of sleep quality on QoL among visitors of lifestyle clinics at the National Guard primary healthcare centers in the Western region of Saudi Arabia in 2023. METHODS: A cross-sectional study was conducted among 369 participants. Data were collected using a questionnaire that addressed sociodemographic characteristics, sleep quality, and perceived QoL. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), while QoL was measured using the Short Form-20 (SF-20) QoL scale. Statistical analysis was performed using SPSS (IBM Corp., Armonk, NY). RESULTS: The median age of participants was 38 years, and the median PSQI score was 9, indicating poor sleep quality. Significant differences in sleep quality were found relating to gender and income. Male gender and low-income status were associated with lower sleep quality. The scores for sleep quality varied between 3 and 16, with a median score of 9, while QoL scores ranged from 34 to 92, with a median score of 72. Good sleep quality was found only among 4.9% of the participants and was associated with higher QoL scores. The correlation between sleep quality and QoL was significant, with a correlation coefficient of -0.399 (p-value < 0.001). CONCLUSION: The study identifies a significant correlation between poor sleep quality and lower QoL among visitors of lifestyle clinics in the Western region of Saudi Arabia. These findings suggest the necessity of addressing sleep quality in interventions aimed at improving overall well-being.

Assessing Self-Rated Physical Health Scores Following Repeat Exposure to Anthropogenic and Natural Hazards in Houston, TX.

BACKGROUND: Research connects health outcomes to hazard exposures but often neglects the nature of the exposure or repeated events. METHODS: We undertook a cross-sectional study (N = 1,094) from a representative sample in the Houston Metropolitan Statistical Area (HMSA). Respondents were recruited using Qualtrics panels, targeting individuals reflecting the population of the HMSA. Physical composite scores (PCS) were calculated using the SF-12v2. RESULTS: Among the hazards (hurricanes, flooding, tornadoes, chemical spills, industrial fires), only chemical spills showed a dose-response: physical health scores declined significantly with repeated exposures. This decline persisted after multiple linear regression. Covariates including sex, race, age, education, and chemical exposure affected PCS, but chemical spill exposure remained the most significant, negatively affecting PCS even after adjusting for other factors (coef =-2.24, 95% CI, -3.33 to -1.15). CONCLUSION: Grasping the effects of hazards, especially repeated ones, can guide emergency management in mitigation, recovery, and preparedness efforts.

Somatisation differentiates fibromyalgia from low back pain: a comparative, cross-sectional cohort study.

OBJECTIVES: To examine whether somatisation, depression, anxiety, fatigue, coping dimensions, pain, physical and social function, or sociodemographic characteristics can differentiate fibromyalgia from low back pain in a cross-sectional cohort setting of our Zurzach Interdisciplinary Pain Programme. METHODS: Fibromyalgia and low back pain (not fulfilling the diagnostic criteria for fibromyalgia) were compared using the Symptom Checklist-90R (SCL-90R) Somatisation scale, the Quantification Inventory for Somatoform Syndromes (QUISS) Number of somatoform symptoms, and other standardised instruments. Standardised mean differences (SMDs) quantified the score differences, and binomial logistic regression modelling with various co-variates differentiated fibromyalgia from low back pain. RESULTS: The largest differences indicating worse health in fibromyalgia (n = 131) were in somatisation (SCL-90R: SMD=-0.971, QUISS: SMD=-0.960), followed by affective health, pain and coping (SMDs between -0.632 and -0.280). Physical and social functioning were comparable in the two conditions (n = 262 low back pain). The two somatisation scales both with odds ratios (OR)=0.966 (p≤ 0.002) plus female sex (OR = 3.396, p< 0.001) predicted 74.3% of the cases correctly (accuracy) with a positive predictive value of 65.3% and a specificity of 87.0% for fibromyalgia. In the female subsample (n = 280), the model remained stable with an accuracy of 71.9%. CONCLUSION: Somatisation stood out from all other somatic, psychosocial, and coping dimensions and sociodemographics as the one significant specific predictor distinguishing fibromyalgia from low back pain. The fibromyalgia phenotype is characterised by the generalisation of painful loci but equally prominently by generalised somatoform symptoms. Assessment of somatisation is recommended to ensure accurate identification and understanding of the multifaceted syndrome of fibromyalgia.

Innovative Therapeutic Delivery of Metastasis-Associated in Colon Cancer 1-Suppressing miRNA Using High Transmembrane 4 L6 Family Member 5-Targeting Exosomes in Colorectal Cancer Mouse Models.

Elevated metastasis-associated in colon cancer 1 (MACC1) expression in colorectal cancer patients, and high transmembrane 4 L6 family member 5 (TM4SF5) protein expressed on various solid tumors' surface, are linked to aggressive cancer behavior and progression. In this study, adipose-derived stem cells (ASCs) were engineered to produce exosomes (Ex) that target the TM4SF5 protein on tumors. Moreover, MACC1-targeting microRNA was encapsulated within the Ex, resulting in TM4SF5-targeting Ex (MACC1-suppressing miRNA; miR-143). The anticancer effects of these Ex were investigated in vitro using the human colorectal cell line HCT116 and in vivo using colorectal cancer mouse xenograft models. In the in vivo assessment, administration of TM4SF5-targeting Ex[miR-143], referred to as tEx[miR-143] herein, resulted in the smallest tumor size, the lowest tumor growth rate, and the lightest excised tumors compared to other treatments (p < 0.05). It also led to the decreased expression of MACC-1 and anti-apoptotic markers MCL-1 and Bcl-xL while inducing the highest expression of pro-apoptotic markers BAX and BIM. These results were consistent with in vitro findings, where t Ex[miR-143] demonstrated the highest inhibition of HCT116 cell migration and invasion. These findings highlight the potential of tEx[miR-143] as an effective therapeutic strategy for colorectal cancer, demonstrating promising results in both targetability and anti-tumor effects in vitro and in vivo, warranting further investigation in clinical settings.

Evaluation of Serum Proteome Sample Preparation Methods to Support Clinical Proteomics Applications.

Serum contains several proteins that are associated with disease-related processes. Mass spectrometry (MS)-based proteomics approaches greatly facilitate serum protein biomarker development. However, the serum proteome complexity presents a technical challenge for the accurate, sensitive, and reproducible quantification of proteins by MS. Thus, efficient sample preparation methods are of critical importance for serum proteome analyses. In this study, we evaluated the technical performance of two serum proteome sample preparation methods using sera from patients with high-grade serous ovarian cancer and patients with benign nongynecological conditions with a goal of providing insight into their compatibility with clinical proteomics workflows. One method entailed the use of immobilized trypsin (SMART Digest Trypsin) with RapiGest SF, an acid-labile surfactant designed to enhance the in-solution enzymatic digestion of proteins. The other method incorporated a commercially available sample preparation kit, iST-BCT, which contains standardized reagents. Significantly higher protein sequence coverage, albeit with lower digestion efficiency, was obtained with the immobilized trypsin + RapiGest SF workflow, whereas the iST-BCT workflow was quicker and had marginally better reproducibility. Protein relative abundance analysis revealed that the serum proteomes clustered primarily by the sample processing workflow and secondarily by disease state. We conducted a time course study to determine whether differences in the relative abundance of diagnostic high-grade serous ovarian cancer serum protein biomarker candidates were biased according to the duration of enzymatic digestion. Our results highlight the importance of optimizing enzymatic digestion kinetics according to the peptide targets of interest while considering the sensitivity of the downstream analytical method utilized in clinical proteomics workflows designed to measure biomarkers.

The association of the comorbidity status of metabolic syndrome and cognitive dysfunction with health-related quality of life.

PURPOSE: Both metabolic syndrome (MetS) and cognitive dysfunction impair health-related quality of life (HRQOL). This study aims to determine whether individuals experiencing both MetS and cognitive dysfunction have lower HRQOL. METHODS: This cross-sectional study enrolled 567 participants who attended outpatient clinics at a medical center in northern Taiwan. MetS was diagnosed according to the modified criteria for the Asian population. Cognitive function was categorized as normal, mild cognitive dysfunction, and advanced cognitive dysfunction according to the score of the Montreal Cognitive Assessment, Taiwanese version. HRQOL was assessed using the SF-36v2® Health Survey (SF-36v2). The associations of the comorbidity status of MetS and cognitive dysfunction with HRQOL were analyzed using linear regression models, adjusting for age, sex, marital status, education level, income groups, and activities of daily living. RESULTS: Out of 567 participants, 33 (5.8%) had MetS with mild cognitive dysfunction, and 34 (6.0%) had MetS with advanced cognitive dysfunction. Participants with both MetS and advanced cognitive dysfunction exhibited the lowest scores in the physical component summary and almost all scales of HRQOL. MetS exacerbated the inverse association between mild cognitive dysfunction and the mental component summary. For those with MetS, the scores on scales of role physical, bodily pain, vitality, and social functioning worsened as cognitive function deteriorated (all Ptrend<0.05). CONCLUSION: As the severity of comorbidity between MetS and cognitive dysfunction varies, patients exhibited poorer performance in different aspects of HRQOL. Future research is needed to find solutions to improve HRQOL for patients with both MetS and cognitive dysfunction.

Research and Analysis on Enhancement of Surface Flashover Performance of Epoxy Resin Based on Dielectric Barrier Discharge Plasma Fluorination Modification.

To conquer the challenges of charge accumulation and surface flashover in epoxy resin under direct current (DC) electric fields, numerous efforts have been made to research dielectric barrier discharge (DBD) plasma treatments using CF4/Ar as the medium gas, which has proven effective in improving surface flashover voltage. However, despite being an efficient plasma etching medium, SF6/Ar has remained largely unexplored. In this work, we constructed a DBD plasma device with an SF6/Ar gas medium and explored the influence of processing times and gas flow rates on the morphology and surface flashover voltage of epoxy resin. The surface morphology observed by SEM indicates that the degree of plasma etching intensifies with processing time and gas flow rate, and the quantitative characterization of AFM indicates a maximum roughness of 144 nm after 3 min of treatment. Flashover test results show that at 2 min of processing time, the surface flashover voltage reached a maximum of 19.02 kV/mm, which is 25.49% higher than that of the untreated sample and previously reported works. In addition to the effect of surface roughness, charge trap distribution shows that fluorinated groups help to deepen the trap energy levels and density. The optimal modification was achieved at a gas flow rate of 3.5 slm coupled with 2 min of processing time. Furthermore, density functional theory (DFT) calculations reveal that fluorination introduces additional electron traps (0.29 eV) and hole traps (0.38 eV), enhancing the capture of charge carriers and suppressing surface flashover.