Assessing suboptimal health status in the Saudi population: Translation and validation of the SHSQ-25 questionnaire.

Background: Suboptimal Health Status (SHS) is realised as a vital feature for improving global health. However, the Arabian world does not have a validated instrument for screening SHS in their population. Therefore, the study aimed to evaluate the psychometric properties of Arabic-translated SHS (ASHSQ-25) in the Saudi Arabian population. Methods: We conducted a cross-sectional study among the conveniently sampled 1590 participants from the Saudi population (with a 97.4% response rate). The data was gathered through an online survey and then exported into SPSS and AMOS version 26.0 for analysis. Mann-Whitney and Kruskal-Wallis tests were used to identify the median difference between demographic groups. The one-tailed 90% upper limit of SHS scores was chosen as the cut-off criteria for SHS. Reliability and confirmatory analysis were performed for the psychometric evaluation of ASHSQ-25 in the Saudi Arabian context. Results: This study demonstrates that the ASHSQ-25 has good internal consistency, interclass correlation coefficient (ICC) = 0.92; 95% confidence interval (CI) = 0.91-0.93) and reliability (Cronbach's α = 0.92). The confirmatory factor analysis (CFA) results indicated a good fit of the databased on the CMIN/degrees of freedom (df) = 4.461, comparative fit index (CFI) = 0.94, Tucker Lewis index (TLI) = 0.93, and Root Mean Square Error of Approximation (RMSEA) = 0.05. The result factor loadings for each item were high (≥ 0.55), except for one item from the immune system subscale. The SHS cut-off point for ASHSQ-25 was 33, leading to a 23.7% prevalence of SHS. Conclusions: This study reveals that ASHSQ-25 has appropriate internal consistency and structural validity to assess SHS in an Arabic-speaking population; therefore, it is recommended.

Psychometric Properties of Suboptimal Health Status Instruments: A Systematic Review.

BACKGROUND: Suboptimal health status (SHS) measurement has now been recognized as an essential construct in predictive, preventive, and personalized medicine. Currently, there are limited tools, and an ongoing debate about appropriate tools. Therefore, it is crucial to evaluate and generate conclusive evidence about the psychometric properties of available SHS tools. OBJECTIVE: This research aimed to identify and critically assess the psychometric properties of available SHS instruments and provide recommendations for their future use. METHODS: Articles were retrieved by following the guidelines of the PRISMA checklist, and the robustness of methods and evidence about the measurement properties was assessed using the adapted COSMIN checklist. The review was registered in PROSPERO. RESULTS: The systematic review identified 14 publications describing four subjective SHS measures with established psychometric properties; these included the Suboptimal Health Status Questionnaire-25 (SHSQ-25), Sub-health Measurement Scale Version 1.0 (SHMS V1.0), Multidimensional Sub-health Questionnaire of Adolescents (MSQA), and the Sub-Health Self-Rating Scale (SSS). Most studies were conducted in China and reported three reliability indices: (1) the internal consistency measured by Cronbach's α value ranged between 0.70 and 0.96; (2) the test-retest reliability; and (3) the split-half reliability coefficient values ranged between 0.64 and 0.98, and between 0.83 and 0.96, respectively. For the values of validity coefficients in the case of SHSQ-25 > 0.71, the SHMS-1.0 ranged from 0.64 to 0.87, and the SSS ranged from 0.74 to 0.96. Using these existing and well-characterized tools rather than constructing original tools is beneficial, given that the existing choice demonstrated sound psychometric properties and established norms. CONCLUSIONS: The SHSQ-25 stood out as being more suitable for the general population and routine health surveys, because it is short and easy to complete. Therefore, there is a need to adapt this tool by translating it into other languages, including Arabic, and establishing norms based on populations from other regions of the world.

Effect of Perceived Self-Vulnerability on Prostate Cancer Screening Uptake and Associated Factors: A Cross-Sectional Study of Public Health Facilities in Western Kenya.

Background: Perceived self-vulnerability to prostate cancer is known to influence screening uptake among men in the general population. However, knowledge gap persists on the influence of perceived self-vulnerability to prostate cancer on uptake of screening among male health workers; a demographic that has health insurance and is assumed to have knowledge of screening services for prostate cancer. Objective: This study aimed to assess the effect of perceived self-vulnerability to prostate cancer on screening uptake among male health workers in Kisumu County, western Kenya. Methods: This was a hospital-based cross-sectional study with a descriptive and analytical design. A modified self-administered questionnaire on self-vulnerability was issued to 197 male health workers who were randomly sampled from a study population of 336 eligible participants. The study was conducted at purposively selected public health facilities. Findings: Level of self-reported screening uptake was 27%. Rural residence (AOR = 0.71: 95% CI, 0.32-1.57, p = 0.019), education level (AOR = 5.01; 95% CI, 1.2-20.86, p = 0.027), participant's lack of knowledge about screening services covered by health insurance schemes of which they are members (AOR = 0.2, 95% CI, 0.08-0.5, p = 0.001), good perception of health status (AOR = 4; 95% CI: 1.52-10.53, p = 005) were determinants of screening uptake for prostate cancer. Perceived self-vulnerability to prostate cancer didn't influence screening uptake of participants (p < 0.05). Participants from rural set-up had a higher likelihood of perceiving themselves to be at risk of prostate cancer (AOR = 2.35, 95% CI, 1.17-4.72, p < 0.05) compared to those form urban settings. Old age of 60 years and above (AOR = 3.5, 95% CI: 0.3-40.98, p < 0.002) was predictive of perceived self-vulnerability. Conclusion: Findings from this study showed low uptake of screening and low perceived self-vulnerability to prostate cancer. Perceived self-vulnerability did not influence screening uptake for prostate cancer. Screening knowledge of prostate cancer as covered by health insurance, good perception of health status and level of education should be integrated in screening programs that are individualized on the basis of personal preferences and informed decision making regarding the uncertainty of benefit and the associated harms of screening.

Association between Cholera Outbreak and Traditional Gold Mining in Northern State, Sudan 2017.

INTRODUCTION: Cholera is one of the health problems causing considerable morbidity and mortality. The Northern State of Sudan experienced a recent cholera outbreak, however, there are limited data on the outbreak. METHODS: The objective of this study was to assess the magnitude and risk factors associated with the cholera outbreak in the Northern State of Sudan. A retrospective case series study was conducted in the Northern State of Sudan, which involved tracing cases of cholera outbreak of 2017. Data were collected through reports and interviews. A geographical information system was used to map all cases during the outbreak. Chi-square test and logistic regression were used to identify associated factors. RESULTS: There were 957 cholera cases reported in the state with an attack rate of 14.2/10,000 persons. Dalgo locality had the highest number (415) of cases reported with an attack rate of 167.2/10,000 persons. About 78% of cases were adult males, while 56.2% of cases were immigrants from other states. Immigrants in Halfa and Dalgo localities were four times (odds ratio [OR] = 4.031, 95% confidence interval [CI]: 2.482-6.547) and eight times (OR = 8.318, 95% CI: 5.674-12.193), respectively, at risk of cholera infection compared to immigrants in Dongola locality. The overall case-fatality rate was 1.9%. This was significantly higher in younger (5.8%) and older (22.7%) age groups (P < 0.05). CONCLUSIONS: The study revealed that the cholera outbreak spread highly along with traditional gold mining areas due to poor sanitation. Therefore, improving sanitation services and establishing an effective surveillance system in these areas are essential to prevent future occurrence of outbreaks.

Gene profiles to characterize the combined toxicity induced by low level co-exposure of silica nanoparticles and benzo[a]pyrene using whole genome microarrays in zebrafish embryos.

Several studies have suggested that air pollutants combine exposure have greater adverse effects. However, limited studies were available on the combined toxicity of silica nanoparticles (SiNPs) and benzo[a]pyrene (B[a]P). The study was to evaluate the toxic effect and mechanisms of low-dose exposure of SiNPs, B[a]P and co-exposure in zebrafish embryos. In this study, zebrafish embryos received intravenous microinjection of SiNPs and B[a]P, and then was used to select differentially expressed genes by microarray analysis. Multiple bioinformatics analyses and STC analysis were done to identify key genes, pathways and biological processes and the expression trend of genes in each group. 1) 3065 differentially expressed genes were identified in zebrafish embryos. 2) These differentially expressed genes were involved in multiple biological processes and cellular processes such as immunity, response to stimuli, cell proliferation, adhesion, signaling transduction, and embryonic development. 3) Dynamic Gene Network analysis was used to identify a subgroup of 26 core genes that involved in multiple biological processes and cellular processes. 4) Pathway analysis and Signal-net analysis indicated that the MAPK signaling pathway, calcium signaling pathway, p53 signaling pathway, PI3k/Akt signaling pathway, and several pathways associated with immune response were the most prominent significant pathways induced by co-exposure of SiNPs and B[a]P in zebrafish embryos. Our study demonstrated that the molecular actions of co-treated with SiNPs and B[a]P on the immune system, inflammatory process and cardiovascular development had more severe toxicity than single exposure.

Low-dose combined exposure of nanoparticles and heavy metal compared with PM2.5 in human myocardial AC16 cells.

The co-exposure toxicity mechanism of ultrafine particles and pollutants on human cardiovascular system are still unclear. In this study, the combined effects of silica nanoparticles (SiNPs) and/or carbon black nanoparticles (CBNPs) with Pb(AC)2 compared with particulate matter (PM)2.5 were investigated in human myocardial cells (AC16). Our study detected three different combinations of SiNPs and Pb(AC)2, CBNPs and Pb(AC)2, and SiNPs and CBNPs compared with PM2.5 at low-dose exposure. Using PM2.5 as positive control, our results suggested that the combination of SiNPs and Pb(AC)2/CBNPs could increase the production of reactive oxygen species (ROS), lactate dehydrogenase leakage (LDH), and malondialdehyde (MDA) and decrease the activities of superoxide dismutase (SOD) and glutathione (GSH); induce inflammation by the upregulation of protein CRP and TNF-α, and apoptosis by the upregulation of protein caspase-3, caspase-9, and Bax while the downregulation of protein Bcl-2; and trigger G2/M phase arrest by the upregulation of protein Chk2 and downregulation of protein Cdc2 and cyclin B1. In addition, the combination of CBNPs and Pb(AC)2 induced a significant increase in MDA and reduced the activities of ROS, LDH, SOD, and GSH, with G1/S phase arrest via upregulation of Chk1 and downregulation of CDK6 and cyclin D1. Our data suggested that the additive interaction and synergistic interaction are the major interaction in co-exposure system, and PM2.5 could trigger more severe oxidative stress, G2/M arrest, and apoptosis than either co-exposure or single exposure.

Fine particle matters induce DNA damage and G2/M cell cycle arrest in human bronchial epithelial BEAS-2B cells.

There is compelling evidence that exposure to particulate matter (PM) is linked to lung tumorigenesis. However, there is not enough experimental evidence to support the specific mechanisms of PM2.5-induced DNA damage and cell cycle arrest in lung tumorigenesis. In this study, we investigated the toxic effects and molecular mechanisms of PM2.5 on bronchial epithelial (BEAS-2B) cells. PM2.5 exposure reduced cell viability and enhanced LDH activity. The cell growth curves of BEAS-2B cells decreased gradually with the increase in PM2.5 dosage. A significant increase in MDA content and a decrease in GSH-Px activity were observed. The generation of ROS was enhanced obviously, while apoptosis increased in BEAS-2B cells exposed to PM2.5 for 24 h. DNA damage was found to be more severe in the exposed groups compared with the control. For in-depth study, we have demonstrated that PM2.5 stimulated the activation of HER2/ErbB2 while significantly upregulating the expression of Ras/GADPH, p-BRAF/BRAF, p-MEK/MEK, p-ERK/ERK, and c-Myc/GADPH in a dose-dependent manner. In summary, we suggested that exposure to PM2.5 sustained the activation of HER2/ErbB2, which in turn promoted the activation of the Ras/Raf/MAPK pathway and the expression of the downstream target c-Myc. The overexpression of c-Myc may lead to G2/M arrest and aggravate the DNA damage and apoptosis in BEAS-2B after exposure to PM2.5.

Cellular pathways involved in silica nanoparticles induced apoptosis: A systematic review of in vitro studies.

Silica nanoparticles (SiNPs) have been found to pass through biological barriers and get distributed in the human body. They induce cell apoptosis via various mechanisms in body organs. To understand these mechanisms, we carried out systematic review of in vitro studies on SiNPs-induced cell apoptosis. Office of Health Assessment and Translation approach for Systematic Review and Evidence Integration was used to identify 14 studies dating from the year 2000 to current. Four studies showed an increase in DNA damage, cell cycle arrest, proapoptotic factors and decrease in antiapoptotic factors resulting to apoptosis. Eight studies showed induction of mitochondrial dysfunction, Bax upregulation, Bcl-2 downregulation, and caspase-3, -7, -9 activities increase. Increase in FADD, TNFR1 and Bid proteins was observed in one study, while the other NO production and caspase-3 activity was increased. These studies found the potency of SiNPs to induce cell apoptosis through DNA damage, mitochondrial, tumor necrosis factor, and nitric oxide related pathways.

Comprehensive gene and microRNA expression profiling on cardiovascular system in zebrafish co-exposured of SiNPs and MeHg.

Air pollution has been shown to increase cardiovascular diseases. However, little attention has been paid to the combined effects of PM and air pollutants on the cardiovascular system. To explore this, a high-throughput sequencing technology was used to determine combined effects of silica nanoparticles (SiNPs) and MeHg in zebrafish. Our study demonstrated that SiNPs and MeHg co-exposure could cause significant changes in mRNA and miRNA expression patterns in zebrafish. The differentially expressed (DE) genes in profiles 17 and 26 of STC analysis suggest that SiNPs and MeHg co-exposure had more proinflammatory and cardiovascular toxicity in zebrafish than single exposure. Major gene functions associated with cardiovascular system in the co-exposed zebrafish were discerned from the dynamic-gene-network, including stxbp1a, celf4, ahr1b and bai2. In addition, the prominently expressed pathway of cardiac muscle contraction was targeted by 3 DE miRNAs identified by the miRNA-pathway-network (dre-miR-7147, dre-miR-26a and dre-miR-375), which included 23 DE genes. This study presents a global view of the combined SiNPs and MeHg toxicity on the dynamic expression of both mRNAs and miRNAs in zebrafish, and could serve as fundamental research clues for future studies, especially on cardiovascular system toxicity.

Telomere Length and Accelerated Biological Aging in the China Suboptimal Health Cohort: A Case-Control Study.

Suboptimal health status (SHS) has been linked to cardiovascular risk factors, psychosocial stress, and unhealthy lifestyle. These factors also contribute to the shortening of telomere length (TL). A case-control study was conducted to examine the association between subjective health measures of SHS from the behavior perspective and also objective measures of TL at molecular level. SHS (cases = 294) was matched by age, sex, and body mass index with ideal health (controls = 294) using a propensity score matching method. Suboptimal health status questionnaire-25 (SHSQ-25) was used in the community-based health survey. A quantitative polymerase chain reaction was used to measure relative telomere length (RTL). Shorter RTL was found among the SHS group compared to the ideal health group (p < 0.05). SHS was almost four times likely to be in the first quartile (odds ratio [OR] = 3.81; 95% confidence interval [CI] 2.21-6.56), almost thrice in second quartile (OR = 2.84; 95% CI 1.65-4.90), and almost twice likely to be in the third quartile (OR = 1.71; 95% CI 1.00-2.94) compared to the fourth quartile (the longest) of RTL after adjusting for socioeconomic, dietary intake, anthropometric, blood pressure, and biochemistry variables (p < 0.05). Notably, SHS score was negatively correlated with RTL (r = -0.218, p < 0.05). Our study confirms an association between SHS and short RTL. Combination of subjective (SHS) and objective (RTL) measures is a novel tool for health aging investigation. Therefore, SHSQ-25 could be used as a screening tool for measuring biological aging in low-income countries at community level where the expensive technique for RTL measurement is not applicable.

Gene expression profiles and bioinformatics analysis of human umbilical vein endothelial cells exposed to PM2.5.

Cardiovascular system is demonstrated the main target of PM2.5 and the objective of this study was to explore the toxic effect and molecular mechanisms caused by PM2.5 in primary human umbilical vein endothelial cells (HUVECs) using microarray and bioinformatics analysis. The results showed that 591 genes were differentially expressed triggered by PM2.5, of which 174 genes were down-regulated, while 417 genes were up-regulated. Gene ontology analysis revealed that PM2.5 caused significant changes in gene expression patterns, including response to stimuli, immune response, and cellular processes. Pathway analysis and Signal-net analysis suggested that endocytosis, chemokine signaling pathway, RNA transport, protein processing in endoplasmic reticulum (ER) and autophagy regulation were the most critical pathways in PM2.5-induced toxicity in HUVECs. Moreover, gene expression confirmation of LIF, BCL2L1, CSF3, HMOX1, RPS6, PFKFB, CAPN1, HSPBP1, MOGS, PREB, TUBB2A, GABARAP by qRT-PCR indicated that endocytosis might be involved in the cellular uptake of PM2.5 by forming phagosomes, and subsequently inflammation, hypoxia and ER stress was occurred, which finally activated autophagy after PM2.5 exposure in HUVECs. In summary, our data can serve as fundamental research clues for further studies of PM2.5-induced toxicity in HUVECs.

1H NMR-based metabolomics study on repeat dose toxicity of fine particulate matter in rats after intratracheal instillation.

Systemic metabolic effects and toxicity mechanisms of ambient fine particulate matter (PM2.5) remain uncertain. In order to investigate the mechanisms in PM2.5 toxicity, we explored the endogenous metabolic changes and possible influenced metabolic pathways in rats after intratracheal instillation of PM2.5 by using a 1H nuclear magnetic resonance (NMR)-based metabolomics approach. Liver and kidney histopathology examinations were also performed. Chemical characterization demonstrated that PM2.5 was a complex mixture of elements. Histopathology showed cellular edema in liver and glomerulus atrophy of the PM2.5 treated rats. We systematically analyzed the metabolites changes of serum and urine in rats using 1H NMR techniques in combination with multivariate statistical analysis. Significantly reduced levels of lactate, alanine, dimethylglycine, creatine, glycine and histidine in serum, together with increased levels of citrate, arginine, hippurate, allantoin and decreased levels of allthreonine, lactate, alanine, acetate, succinate, trimethylamine, formate in urine were observed of PM2.5 treated rats. The mainly affected metabolic pathways by PM2.5 were glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, citrate cycle (TCA cycle), nitrogen metabolism and methane metabolism. Our study provided important information on assessing the toxicity of PM2.5 and demonstrated that metabolomics approach can be employed as a tool to understand the toxicity mechanism of complicated environmental pollutants.

Genome-wide transcriptional analysis of cardiovascular-related genes and pathways induced by PM2.5 in human myocardial cells.

Air pollution has been a major environment-related health threat. Most of the studies on PM2.5 toxicity have verified on the cardiovascular system and endothelial cells. However, researches on PM2.5-induced myocardial-related toxicity are limited. This study aims to fully understand the toxic effects of PM2.5 on human myocardial cell (AC16) and explore its molecular mechanism based on microarray analysis and bioinformatics analysis. Microarray data analysis manifested that PM2.5-induced toxicity affected expression of 472 genes compared with the control group, including 166 upregulated genes and 306 downregulated genes in human myocardial (AC16) cells. GO analysis showed that cellular processes such as immune response, cell maturation, embryonic heart tube morphogenesis, cellular response to electrical stimulus, skeletal muscle tissue regeneration, and negative regulation of signal transduction were upregulated, while regulation of transcription (DNA-dependent), rhythmic process, protein destabilization apoptotic process, and innate immune response were downregulated. The pathway analysis indicates that cell signaling pathways such as cytokine-cytokine receptor interaction, NF-κB signaling pathway, chemokine signaling pathway, endocrine and other factor-regulated calcium reabsorption, HTLV-I infection, and cell adhesion molecules (CAMs) were upregulated, while the TGF-ß signaling pathway was downregulated. In addition, Signal-net showed that the TUBA4A, ADRBK2, BRIX1, SMC4, EIF5B, PRMT1, ATG4B, and NDC80 genes were significantly decreased, while the expression of the KRT6B gene was markedly increased compared with the control group. All the genes were verified by qRT-PCR. This study had provided new bioinformatics evidences in PM2.5-induced myocardial tissue toxicity which is necessary for further cardiovascular system toxicity studies.

Combined Effect of Silica Nanoparticles and Benzo[a]pyrene on Cell Cycle Arrest Induction and Apoptosis in Human Umbilical Vein Endothelial Cells.

Particulate matter (PM) such as ultrafine particulate matter (UFP) and the organic compound pollutants such as polycyclic aromatic hydrocarbon (PAH) are widespread in the environment. UFP and PAH are present in the air, and their presence may enhance their individual adverse effects on human health. However, the mechanism and effect of their combined interactions on human cells are not well understood. We investigated the combined toxicity of silica nanoparticles (SiNPs) (UFP) and Benzo[a]pyrene (B[a]P) (PAH) on human endothelial cells. Human umbilical vascular endothelial cells (HUVECs) were exposed to SiNPs or B[a]P, or a combination of SiNPs and B[a]P. The toxicity was investigated by assessing cellular oxidative stress, DNA damage, cell cycle arrest, and apoptosis. Our results show that SiNPs were able to induce reactive oxygen species generation (ROS). B[a]P, when acting alone, had no toxicity effect. However, a co-exposure of SiNPs and B[a]P synergistically induced DNA damage, oxidative stress, cell cycle arrest at the G2/M check point, and apoptosis. The co-exposure induced G2/M arrest through the upregulation of Chk1 and downregulation of Cdc25C, cyclin B1. The co-exposure also upregulated bax, caspase-3, and caspase-9, the proapoptic proteins, while down-regulating bcl-2, which is an antiapoptotic protein. These results show that interactions between SiNPs and B[a]P synergistically potentiated toxicological effects on HUVECs. This information should help further our understanding of the combined toxicity of PAH and UFP.

Co-exposure to amorphous silica nanoparticles and benzo[a]pyrene at low level in human bronchial epithelial BEAS-2B cells.

Both ultrafine particles (UFP) and polycyclic aromatic hydrocarbons (PAHs) are widely present in the environment, thus increasing their chances of exposure to human in the daily life. However, the study on the combined toxicity of UFP and PAHs on respiratory system is still limited. In this study, we examined the potential interactive effects of silica nanoparticles (SiNPs) and benzo[a]pyrene (B[a]P) in bronchial epithelial cells (BEAS-2B). Cells were exposed to SiNPs and B[a]P alone or in combination for 24 h. Co-exposure to SiNPs and B[a]P enhanced the malondialdehyde (MDA) contents and reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities significantly, while the reactive oxygen species (ROS) generation had a slight increase in the exposed groups compared to the control but not statistically significant. Cell cycle arrest induced by the co-exposure showed a significant percentage increase in G2/M phase cells and a decrease in G0/G1 phase cells. In addition, there was a significant increase in BEAS-2B cells multinucleation as well as DNA damage. Cellular apoptosis was markedly increased even at the low-level co-exposure. Our results suggest that co-exposure to SiNPs and B[a]P exerts synergistic and additive cytotoxic and genotoxic effects.

Glycan Biomarkers for Rheumatoid Arthritis and Its Remission Status in Han Chinese Patients.

Rheumatoid arthritis (RA), a systemic, chronic, and progressive inflammatory autoimmune disease, affects up to 1.0% of the world population doubling mortality rate of patients and is a major global health burden. Worrisomely, we lack robust diagnostics of RA and its remission status. Research with the next-generation biomarker technology platforms such as glycomics offers new promises in this context. We report here a clinical case-control study comprising 128 patients suffering from chronic RA (80.22% in remission, 19.78% active clinically) and 195 gender- and age-matched controls, with a view to the putative glycan biomarkers of RA as well as its activity or remission status in Han Chinese RA patients. Hydrophilic interaction liquid chromatography-ultra-performance liquid chromatography (HILIC-UPLC) was used for the analysis of IgG glycans. The regression model identified the glycans that predict RA status, while a receiver operating characteristic (ROC) curve analysis validated the sensitivity and prediction power. Among the total 24 glycan peaks (GP1-GP24), ROC analysis showed only GP1 prediction to be highly sensitive with an area under the curve (AUC) = 0.881. Even though GP21 and GP22 could predict active status among the RA cases (p < 0.05), they had lower sensitivity of prediction with an AUC = 0.658. Taken together, these observations suggest that GP1 might have potential as a putative biomarker for RA in the Han Chinese population, while the change in IgG glycosylation shows association with the RA active and remission states. To the best of our knowledge, this is the first glycomics study with respect to disease activity and remission states in RA.