Critical Risk Factor Research Articles

Hippocampal microRNA-26a-3p deficit contributes to neuroinflammation and behavioral disorders via p38 MAPK signaling pathway in rats

BackgroundNeuronal injury is considered a critical risk factor in the pathogenesis of most neurological and neuropsychiatric diseases. However, the underlying molecular mechanisms and identification of potential therapeutic targets for preventing neuronal injury associated with brain function remain largely uncharacterized. Therefore, identifying neural mechanisms would put new insights into the progression of this condition and provide novel therapeutic strategies for the treatment of these diseases.MethodsStereotactic injection of AAV virus was used to knock-down the miR-26a-3p within hippocampus of rats. Behavioral changes was detected by open field test (OFT), elevated plus maze (EPM), forced swim test (FST) and sucrose preference test (SPT). The inflammatory cytokines and related proteins were verified by real-time quantitative PCR, immunoblotting or immunofluorescence assay. Golgi staining and electron microscopy analysis was used to observe the dendritic spine, synapse and ultrastructural pathology. SB203580 (0.5 mg/kg) were administered daily to prevent p38 MAPK via an intraperitoneal (i.p.) injection. Finally, electrophysiological method was used to examine the synaptic transmission via whole-cell patch-clamp recording.ResultsHere, we showed that miR-26a-3p deficiency within hippocampal regions leads to the activation of microglia, increased level of pro-inflammatory cytokines and behavioral disorders in rats, effects which appear to be mediated by directly targeting the p38 mitogen-activated protein kinase (MAPK)–NF-κB signaling pathway. Specifically, we found that the enhanced glia-activation may consequently result in neuronal deterioration that mainly presented as the dysregulation of structural and functional plasticity in hippocampal neurons. In contrast, preventing p38 pathway by SB203580 significantly ameliorated abnormal behavioral phenotypes and neuronal jury resulting from miR-26a-3p knock-down.ConclusionThese results suggest that the normal expression of miR-26a-3p exerts neuroprotective effects via suppressing neural abnormality and maintaining neuroplasticity to against behavioral disorders in rats. These effects appear to involve a down-regulation of p38 MAPK-NF-κB signaling within the hippocampal region. Taken together, these findings provide evidence that miR-26a-3p can function as a critical factor in regulating neural activity and suggest that the maintaining of normal structure and function of neurons might be a potential therapeutic strategy in the treatment of neurological disorders.Graphical

Association of Kidney Function with Risk of Incident Dementia: A Prospective Cohort Study of 275,167 UK Biobank Participants.

Previous studies have reported inconsistent associations between chronic kidney disease (CKD) and dementia. To evaluate whether CKD is a risk factor for dementia and compare the performance of different measures of calculating estimated glomerular filtration rate (eGFR). 275,167 participants from UK Biobank were included and eGFR at baseline was calculated using serum creatinine (eGFRcr), cystatin C (eGFRcys), and creatinine-cystatin C equations (eGFRcr-cys). Restricted cubic splines and Cox regression models were performed to assess the relationship of eGFR with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). We observed a U-shaped relationship between each eGFR and risk of all-cause dementia and VaD, with eGFRcys and eGFRcr-cys showing a closer linkage (peGFRcys <0.0001, peGFRcrhboxcys<0.0001 and peGFRcr = 0.0001). Lower and supranormal eGFR were related to increased risk of all-cause dementia. Compared to the reference category of 90-104 ml/min/1.73 m2, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause dementia for eGFRcr-cys 30-59, <30, and ≥105 ml/min/1.73 m2 were 1.26 (95% CI [1.05-1.50], p = 0.012), 2.62 (95% CI [1.54-4.47], p < 0.001), and 1.41 (95% CI [1.17-1.70], p < 0.001). No statistically significant association was observed between eGFR with risk of AD. This prospective study identified impaired kidney function as a critical risk factor for dementia and noted the application of cystatin C strengthened the relationship between CKD and dementia, underlining the significant value of preserving kidney function to reduce the risk of dementia and considering cystatin C measurement as part of clinical practice.

Resveratrol attenuates cigarette smoke extract induced cellular senescence in human airway epithelial cells by regulating the miR-34a/SIRT1/NF-κB pathway.

Chronic obstructive pulmonary disease (COPD) is characterized by accelerated lung aging. Smoking is the critical risk factor for COPD. Cellular senescence of airway epithelial cells is the cytological basis of accelerated lung aging in COPD, and the regulation of microRNAs (miRNAs) is the central epigenetic mechanism of cellular senescence. Resveratrol (Res) is a polyphenol with anti-aging properties. This study investigated whether Res attenuates cigarette smoke extract (CSE)-induced cellular senescence in human airway epithelial cells (BEAS-2B) through the miR-34a/SIRT1/nuclear factor-kappaB (NF-κB) pathway. BEAS-2B cells were treated with Res, CSE and transfected with miR-34a-5p mimics. Cellular senescence was evaluated by senescence -related β-galactosidase (SA-β-gal) staining and expression of senescence-related genes (p16, p21, and p53). The expressions of miR-34a-5p, SIRT1, and NF-κB p65 were examined using quantitative real time polymerase chain reaction and western blotting. The senescence-associated secretory phenotype (SASP) cytokines (IL-1β, IL-6, IL-8, TNF-α) were assessed by enzyme-linked immunosorbent assay. The binding between miR-34a-5p and SIRT1 was confirmed by dual-luciferase reporter assay. The results showed that CSE dose-dependently decreased cell viability and elevated cellular senescence, characterized by increased SA-β-gal staining and senescence-related gene expressions (p16, p21, and p53). Further, CSE dose-dependently increased the expression of miR-34a-5p and SASP cytokines (IL-1β, IL-6, IL-8, TNF-α) in BEAS-2B cells. Pretreatment with Res inhibited CSE-induced cellular senescence and secretion of SASP cytokines (IL-1β, IL-6, IL-8, TNF-α) in a dose-dependent manner. Moreover, Res reversed the CSE-induced down-regulation of SIRT1 and up-regulation of miR-34a-5p and NF-κB p65. SIRT1 is a target of miR-34a-5p. Overexpression of miR-34a-5p via transfection with miR-34a-5p mimic in BEAS-2B cells attenuated the inhibitory effect of Res on cellular senescence, accompanied by reversing the expression of SIRT1 and NF-κB p65. In conclusion, Res attenuated CSE-induced cellular senescence in BEAS-2B cells by regulating the miR-34a/SIRT1/NF-κB pathway, which may provide a new approach for COPD treatment.

Association between migraine or severe headache and hypertension among US adults: A cross-sectional study

Background and aimsEpidemiological evidence of the association between migraines, severe headaches, and hypertension is contradictory. Hypertension is a critical risk factor for cardiovascular diseases. Migraine is a common neurological disease and a major cause of disability worldwide. Therefore, we aimed to investigate the relationship between migraine, severe headaches, and hypertension among US adults. Methods and resultsCross-sectional data from 5716 subjects were obtained from the National Health and Nutrition Examination Survey between 1999 and 2004. Weighted logistic regression models investigated the association between migraines, severe headaches, and hypertension. In total, 5716 subjects were enrolled in the present study, of whom 1134 (19.8%) had migraine or severe headaches. Participants with migraine were predominantly younger females and had a higher body mass index (BMI), lower educational level, lower dietary intake of potassium and calcium, lower serum levels of total cholesterol (TC), creatinine, and hemoglobin, as well as a higher estimated glomerular filtration rate (eGFR) (all P < 0.05). After fully adjusting for potential confounders, migraine or severe headaches were positively associated with hypertension (OR 1.25, 95% CI: 1.03–1.53). ConclusionOur study found a positive association between migraine, severe headaches, and hypertension. Further studies are needed to verify the causality of this association and elucidate the underlying mechanisms.

Loss of GNE Predicts Lymph Node Metastasis in Early Gastric Cancer.

Endoscopic surgery is increasingly utilized for the treatment of early gastric cancer (EGC) worldwide, whereas lymph node metastasis (LNM) remains a critical risk factor for the relapse of EGC after endoscopic surgery. Therefore, identifying potential predictive factors and understanding the molecular mechanisms are urgently needed for improving the outcome of EGC patients with LNM. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme in the process of biosynthesis of CMP-Neu5Ac from UDP-N-acetylglucosamine (UDP-GlcNAc), which acts as a substrate for several reactions in glycan metabolism. In this study, we found that GNE was down-regulated in EGC patients with LNM. GNE expression as well as localization, tumor size, intravascular tumor thrombi and Lauren's classification were further identified as independent predictive factors for LNM. Combining GNE expression with traditional risk factors, including tumor size and differentiation degrees, could generate a better model for predicting LNM in EGC patients. Overall, our study implies that low GNE expression is a potential predictor of LNM in EGC.

Rate and Risk Factors of Acute Myocardial Infarction after Debut of Chronic Kidney Disease-Results from the KidDiCo.

Chronic kidney disease (CKD) is a known risk factor for cardiovascular disease, including acute myocardial infarction. However, whether this risk is only associated with severe kidney disease or is also related to mildly impaired kidney function is still under debate. The incidence rate and risk factors of incident acute myocardial infarction (AMI) in patients with CKD are sparse. Potential differences in risk factor profiles between CKD patients with incident AMI and CKD patients with a prior AMI have not been sufficiently investigated. Furthermore, important factors such as albuminuria and socio-economic factors are often not included. The primary aim of this study was to establish the incidence rate of AMI after CKD debut. Secondly, to evaluate the importance of different CKD stages and the risk of having an AMI. Finally, to identify individuals at risk for AMI after CKD debut adjusted for prevalent AMI. Based on data from the kidney disease cohort of Southern Denmark (KidDiCo), including 66,486 CKD patients, we established incidence rates and characteristics of incident AMI among patients within a 5-year follow-up period after CKD debut. A Cox regression was performed to compute the cause-specific hazard ratios for the different risk factors. The incidence rate for CKD stage G3-5 patients suffering acute myocardial infarction is 2.5 cases/1000 people/year. In patients without a previous myocardial infarction, the risk of suffering a myocardial infarction after CKD debut was only significant in CKD stage G4 (HR = 1.402; (95% CI: 1.08-1.81); p-value = 0.010) and stage G5 (HR = 1.491; (95% CI: 1.01-2.19); p-value = 0.042). This was not the case in patients who had suffered an acute myocardial infarction prior to their CKD debut. In this group, a previous myocardial infarction was the most critical risk factor for an additional myocardial infarction after CKD debut (HR = 2.615; (95% CI: 2.241-3.05); p-value &lt; 0.001). Irrespective of a previous myocardial infarction, age, male sex, hypertension, and a low educational level were significant risk factors associated with an acute myocardial infarction after CKD debut. The incidence rate of AMI in patients with CKD stage G3-5 was 2.5 cases/1000 people/year. Risk factors associated with incident AMI in CKD stage G3-5 patients were CKD stage, age, and hypertension. Female sex and higher educational levels were associated with a lower risk for AMI. Prior AMI was the most significant risk factor in patients with and without previous AMI before fulfilling CKD stage G3-5 criteria. Only age, sex, and a medium-long educational level were significant risk factors in this group.

Abstract 13600: Performance of a Multi-Metabolite Score Added to a Risk Prediction Model for Incident Diabetes in Young Adults: The CARDIA Study

Introduction: The Finnish Diabetes Risk Score (FINDRISC) is a risk prediction tool used to estimate absolute risk for type 2 diabetes mellitus (DM), a critical risk factor for cardiovascular disease. The Diabetes Risk Index (DRI) is a multi-metabolite DM risk score developed by combining the Lipoprotein Insulin Resistance Index (LP-IR), calculated from six lipoproteins, and the branched chain amino acids, valine and leucine. Although the DRI is independently associated with future DM in middle-aged adults, the performance of this novel biomarker when added to FINDRISC to predict incident DM in young adults is not known. Hypothesis: The addition of DRI to FINDRISC will improve the 10-year(y) risk prediction of DM across all ages in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Methods: We measured the DRI using NMR spectroscopy in CARDIA participants across different age categories: 20-30y (n=1,911), 30-40y (n=2,716), 40-50y (n=2,232). We used Cox proportional hazards regression to evaluate the association of the DRI with incident 10-y DM risk. We assessed FINDRISC model performance using C-statistic and continuous Net Reclassification Index (NRI) with and without the addition of the DRI as a covariate. Results: DRI was associated with 10-y DM risk across all age categories. Addition of the DRI modestly improved the C-statistic in the 30-40-y age category. Addition of DRI to FINDRISC improved the overall NRI in the 30-40- and 40-50-y age categories. The non-event NRI was significant across all 3 age categories and reclassified 25-36% of participants who did not develop DM to a lower estimate of incident DM risk (Table). Conclusions: Among young and middle-aged adults, DRI scores were associated with 10-y risk of DM. The addition of DRI to FINDRISC led to improvements in reclassification of DM risk, as the addition of DRI to FINDRISC correctly classified up to 36% of participants who did not develop DM (over 10y) to a lower estimate of incident DM risk.

Abstract 13054: The Novel Galnac-Conjugated Rnai Trigger Downregulates Apoc3 and Triglyceride Levels in Humanized Liver Mouse Model

Background: Hypertriglyceridemia is a critical risk factor for coronary artery disease. Apolipoprotein C-III (APOC3), produced by liver hepatocytes, regulates triglyceride (TG) levels. We studied effect of novel GalNAc-conjugated APOC3 targeting RNAi trigger (STP125G) on APOC3 and TG levels in humanized liver mouse model. Methods: In dose response study, female uPA-SCID mice (n=4 mice/group), group 1 received PBS control, group 2 received 10mg/kg and group 3 received 30mg/kg STP125G, subcutaneously on day 0. Liver biopsies, plasma and serum samples were collected at week 2. In duration response study, male uPA-SCID mice (n=4 mice/group/timepoint), group 1 received PBS control and group 2 received 10mg/kg STP125G, subcutaneously on day 0. Liver biopsies, plasma and serum samples were collected for each group at weeks 2, 4, 8 and 12. Human APOC3 mRNA (qPCR) and protein (ELISA) levels were measured in liver biopsies and plasma samples, respectively. TGs and total cholesterol (TC) levels were measured in serum samples. Results: In dose response study, animals reported significant suppression of mRNA and reduction of plasma protein levels in 10mg/kg (88% and 91%, respectively) and 30mg/kg (92% and 98%, respectively) dose groups as compared to control group ( p &lt;0.001). Animals also reported significant reductions in TGs and TC levels at 10mg/kg (25% and 33%, respectively) and 30mg/kg (43% and 44%, respectively) dose groups as compared to control group ( p &lt;0.05). In duration response study, treated animals reported significant suppression of mRNA levels at week 2 (83%), week 4 (85%) and week 8 (48%) as compared to control group ( p &lt;0.0001). Treated animals reported significant reduction in plasma protein levels at week 2 (82%; p &lt;0.0001), week 4 (89%; p &lt;0.0001) and week 8 (70%; p =0.0005) as compared to control group. At week 4, treated animals reported significant reduction in TGs (53%; p=0.0079) and TC (36%; p=0.0072). Conclusions: The studies demonstrated that a single administration of STP125G, in a humanized liver mouse model, results in significant suppression of human APOC3 mRNA and plasma protein levels that lasts for up to 8 weeks. It also suggests treatment with STP125G results in lowering of triglycerides and total cholesterol in the treated animals.

Temporal and spatial pattern of dust storms, their polycyclic aromatic hydrocarbons, and human health risk assessment in the dustiest region of the world.

This study evaluated the concentration and health risks of polycyclic aromatic hydrocarbons (PAHs) in Abadan City under 4 different climatic conditions: normal days, dusty days, dust with northwesterly winds, and dust with southeasterly winds. It also determined the sources of aromatics and discussed the relationship between meteorological parameters and PAH concentrations. The spatiotemporal distribution of dust in the area was determined using the HYSPLIT (hybrid single-particle Lagrangian integrated trajectory) back trajectory model, moderate resolution imaging spectroradiometer (MODIS) images. For this purpose, sampling was performed for 70days using an Omni device. The concentrations of 16 PAHs (USEPA) ranged from 46.22 to 90.96ng/m3. The highest concentration of high molecular weight (HMW) PAHs was 4-6 rings, of which 4 rings were predominant in all samples. PAH sources were identified using diagnostic ratios and principal component analysis (PCA), and it was shown that PAHs mainly originate from a mixture of sources, including vehicular emissions, petrol emissions, and traffic. Wind speed was negatively correlated with dust, except on dusty days. This result indicates a decrease in PAH concentrations when wind speed increases. On the other hand, the dust correlation with PAH was positive on normal days, but a negative correlation was observed on dusty days. This result was due to the lower concentration of PAHs from natural resources (such as dust source areas) vs. human resources (such as traffic and industry). PAH health risk assessment in Abadan City showed that the risk of carcinogenesis was higher on normal days and through skin contact. The probability of incremental lifetime cancer risk (ILCR) in all sampling conditions was potential in terms of carcinogenic risk (10-4-10-6). As a critical risk factor, relevant authorities should prevent, control, and reduce it.

Determining the critical risk factors for predicting the severity of ship collision accidents using a data-driven approach

Ship collision accidents often result in serious casualties and property losses. Predicting the severity of ship collisions is beneficial to improve maritime transport safety. Therefore, this study proposes a data-driven approach integrating association rule mining (ARM), complex network (CN), and random forest (RF) to explore the correlation among risk factors and determine the critical risk factors for predicting the severity of ship collision accidents. Specifically, ARM is integrated with CN to develop the risk interaction network of ship collisions and to identify the criticality of risk factors. Then, RF is employed to predict the severity of ship collisions, and determine the risk factors that have a critical effect on severity prediction. The results show that poor team communication is the most critical risk factor for predicting the severity of ship collisions. Moreover, the criticality of risk factors is different in the risk networks and prediction model. Results from this study would help relevant stakeholders to assess current risks and tailor safety strategies to reduce the severity of ship collisions.

Safety Workplace: The Prevention of Industrial Security Risk Factors

“To earn a living”. The definition of work and our understanding of the workplace have changed in recent years due to the emergence of occupational health and is now a field of study under continuous improvement. Despite the fact that there is a huge amount of information, studies, and guidance about how to improve occupational security, the factors that must be considered in a workplace as real hazards to avoid in order to achieve a truly healthy workplace are always subject to debate. This research contributes to efforts in two important ways. The first goal assesses the information about security risk factors established and mentioned by official international institutions aimed at safety and security science by using the relationship and categorization between the identified risks during work activities performance. The second goal is to establish the necessary requirements to be fulfilled to ensure that a workplace will be considered “healthy and safe”. As a result, it is defined that the lack of ergonomics represents the most critical risk factor in order to reduce the incidence of work-related illness during the design and continuous improvement of a tailored workplace.

Botanical Antcin K Alleviates High-Fat Damage in Palm Acid Oil-Treated Vascular Endothelial Cells and Macrophages.

Lipid metabolism disorder is the most critical risk factor for atherosclerosis, and the process involves lipid deposition in the arterial intima. In Taiwan, antcin K, an active triterpenoid from the fruiting bodies of Antrodia camphorata, has been considered a potential lipid-lowering agent. Despite this, the possible therapeutic mechanisms of antcin K remain unclear. To explore the crucial role of botanical antcin K in reducing atherosclerotic plaque, we used SVEC4-10 vascular endothelial cells and RAW264.7 macrophages with palm acid oil-induced high-fat damage as our cell models. Our results showed through using the DPPH assay that antcin K had excellent free radical scavenging ability. Antcin K treatment can significantly alleviate the high-fat damage and reduce the levels of inflammatory factors of TNF-α and IL-1β in vascular endothelial cells and macrophages, as shown through MTT assay and ELISA. Furthermore, antcin K treatment can effectively enhance migration ability and clear lipid deposition in macrophages, as shown by using cell migration assay and oil red O staining. When stained with immunofluorescence, antcin K was shown to significantly decrease the expression of adhesion molecules of vascular cell adhesion molecule 1 (VCAM-1) in vascular endothelial cells involved in monocyte migration and inflammation. Antcin K not only reduced the expression of the CD36 scavenger receptor but also augmented the expression of Kruppel-like factor 4 (KLF4) transcription factor in macrophages, which inhibits the transformation of macrophages into foam cells underlying the pathological process of atherosclerosis. Taking our findings into account, we suggested that botanical antcin K could have therapeutic potential for the treatment of atherosclerosis.

Analytical Methods for Physicochemical Characterization and Toxicity Assessment of Atmospheric Particulate Matter: A Review

Particle-bound pollutants are a critical risk factor for human respiratory/cardiovascular conditions. A comprehensive analysis of the physicochemical characteristics of PM is often challenging since it requires combining different practical methods with a good understanding the of characterization outputs. The present review aims to (1) provide a comprehensive assessment of the underlying mechanisms of PM cytotoxicity and the related biological response; (2) evaluate the selected methods for PM characterization in terms of outputs, technical aspects, challenges, and sample preparation; (3) present effective means of studying PM physicochemical toxicity and composition; and (4) provide recommendations for enhancing the human health risk assessment. The cellular response to potentially toxic elements in PM is complex to understand as exposure includes systemic inflammation, increased ROS accumulation, and oxidative stress. A comprehensive toxicity assessment requires blending morphological features and chemical composition data. For the morphological/chemical characterization, we recommend first using SEM-EDS as a practical method for the single-particle analysis. Then, the bulk chemistry of PM can be further studied using either a dry analysis (e.g., XRF) or wet analysis techniques (e.g., ICP and IC). Finally, when used on a need basis, the reviewed complementary laboratory methods may further add valuable information to the characterization. The accuracy of the human health risk assessment may be improved using bioaccessible/soluble fractions of the contaminants instead of the total contaminant concentration. Having an integrated understanding of the covered analytical methods along with the health risk assessment guidelines would contribute to research on atmospheric chemistry, molecular biology, and public health while helping researchers better characterize human exposure to PM and the associated adverse health effects.

Ginsenoside Rg1 Inhibits STAT3 Expression by miR-15b-5p to Attenuate Lung Injury in Mice with Type 2 Diabetes Mellitus-Associated Pulmonary Tuberculosis.

Type 2 diabetes mellitus (T2DM) has been regarded as a critical risk factor for pulmonary tuberculosis (PTB). Ginsenoside Rg1 has been identified as a potential therapeutic agent for T2DM by suppressing the inflammatory response. However, the effect of Rg1 on T2DM-associated PTB has not been reported. In this study, we aimed to explore the function of Rg1 in the regulation of T2DM-associated PTB. We established a T2DM-associated PTB mouse model and found that the fibrosis of lung tissues was inhibited by Rg1 in T2DM-associated PTB mice. The lung injury of T2DM-associated PTB mice was repressed by Rg1. Moreover, the levels of IL-6, TNF-α, and IL-1β in the lung tissues and serum were decreased by Rg1 in T2DM-associated PTB mice. The treatment with Rg1 inhibited the levels of free fatty acid and enhanced the expression of miR-15b-5p in lung tissues of T2DM-associated PTB mice. MiR-15b-5p targeted and inhibited the STAT3 expression. The expression of STAT3 was downregulated by Rg1, while the inhibition of miR-15b-5p reversed the downregulation. The expression of miR-15b-5p was reduced, but the expression of STAT3 was upregulated in the lung tissues of T2DM-associated PTB mice. We validated that miR-15b-5p attenuated inflammation and lung injury in the T2DM-associated PTB mouse model. The overexpression of STAT3 or the suppression of miR-15b-5p restored lung fibrosis and injury inhibited by Rg1 in T2DM-associated PTB mice. Meanwhile, the Rg1-repressed levels of IL-6, TNF-α, and IL-1β were enhanced by the overexpression of STAT3 or the suppression of miR-15b-5p. In addition, the levels of free fatty acid repressed by Rg1 were reversed by STAT3 overexpression and miR-15b-5p inhibition. Thus, we conclude that ginsenoside Rg1 inhibits the STAT3 expression by miR-15b-5p to attenuate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis.

Carbon monoxide monitoring to objectively measure smoking status in cardiac rehabilitation.

Participation in cardiac rehabilitation (CR) is associated with reduced morbidity and mortality. However, most programs rely on self-report measures when assessing the critical risk factor of smoking. This study examined smoking status using self-report versus objective measurement using expired carbon monoxide (CO) and compared patient characteristics by CO level. Patients were screened for smoking status when entering CR by self-report and by objectively measured CO. Measures of aerobic fitness, educational attainment, depressive symptoms, and self-reported physical function were also collected. The discrepancy between smoking status based on self-report and objective measurement was examined and patient characteristics by CO measurement were compared. Of the 853 patients screened, 62 self-reported current smoking and 112 had a CO of ≥ 4 ppm. Using a cut-off of ≥ 4 ppm encompassed almost all self-reported smokers (specificity: 98.5%) and identified 61 patients (not reporting current smoking) needing further screening. Further questioning yielded an additional 21 patients with combusted use (tobacco/cannabis), six nonsmoking patients with environmental CO exposure, and 34 where the reason for elevated CO was unknown. CO ≥ 4 ppm patients were younger (62.2 vs. 67.7, p < .01), had higher depression scores (5.6 vs. 3.7, Patient Health Questionairre-9, p < .01), had lower educational attainment (59.0% ≤ high school vs. 31.3%, p < .01), had lower levels of fitness (after controlling for clinical characteristics, p < .01), and completed fewer CR sessions (18 vs. 22, p < .01). A substantial number of patients who are actively smoking may be misclassified by relying on patient report alone. CO monitoring provides a simple and objective method of systematically screening patients. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Identification and Evaluation of Risks Encountered in BOT Type Transportation Projects in Turkey: Case Studies

Yap-İşlet-Devret modeli (YİD) ile kamu hizmetlerinin sağlanmasında dünyada öncü ülkelerden olan Türkiye’de, giderek artan kentsel nüfusa bağlı olarak özellikle ulaştırma yatırımlarına olan ihtiyaç artmaktadır. YİD modelleri, bünyesinde projenin başarısını etkileyen çok sayıda riski barındırmaktadır. Bu risklerin tanımlanması; tanımlanan risklere yönelik yanıtların geliştirilerek doğru risk paylaşımlarının yapılabilmesi için önem arz etmektedir. Çalışmada, Türkiye’de YİD modeliyle gerçekleştirilmiş üç güncel ulaştırma projesinde karşılaşılan risklerin tanımlanması ve tartışılması amaçlanmıştır. Çalışmanın sonucunda; üç projede ortak olarak, finansman temini ile ilgili ve fizibilite çalışmalarının yetersizliğinden kaynaklanan problemler nedeniyle projelerin kapsamında ve tarafların risk paylaşımlarında değişikliklere gitmek durumunda kalındığı anlaşılmıştır. Yaşanan problemlere rağmen projelerin kararlılıkla hayata geçirilmesi, ülkede YİD projelerine yönelik güçlü bir politik desteğin olduğunu göstermektedir. Ancak, YİD projeleri için en kritik risk faktörü olan “öngörülen piyasa talebine ulaşılamaması”, bu projelerde de söz konusu olmuştur. Yol projelerinde, geçiş ücretleri ve farklı alternatiflerin bulunması talebi etkilemiş olup; projeler tamamlandıktan kısa süre sonra ortaya çıkan Covid-19 salgınına bağlı dünya genelindeki kapanmaların, beklenen gelirlerin sağlanamamasının esas nedeni olduğu düşünülmektedir. Türkiye’deki YİD ulaştırma projelerinin fizibilite aşamasında çevresel, teknik ve ekonomik açılardan kapsamlı olarak değerlendirilmesi; yapım ve işletme süresince karşılaşılan problemlerin minimuma indirilmesinde temel teşkil etmektedir.

Excess diabetes mellitus-related deaths during the COVID-19 pandemic in the United States.

BackgroundDiabetes mellitus (DM) is a critical risk factor for severe SARS-CoV-2 infection, and SARS-CoV-2 infection contributes to worsening glycemic control. The COVID-19 pandemic profoundly disrupted the delivery of care for patients with diabetes. We aimed to determine the trend of DM-related deaths during the pandemic.MethodsIn this serial population-based study between January 1, 2006 and December 31, 2021, mortality data of decedents aged ≥25 years from the National Vital Statistics System dataset was analyzed. Decedents with DM as the underlying or contributing cause of death on the death certificate were defined as DM-related deaths. Excess deaths were estimated by comparing observed versus expected age-standardized mortality rates derived from mortality during 2006-2019 with linear and polynomial regression models. The trends of mortality were quantified with joinpoint regression analysis. Subgroup analyses were performed by age, sex, race/ethnicity, and state.FindingsAmong 4·25 million DM-related deaths during 2006-2021, there was a significant surge of more than 30% in mortality during the pandemic, from 106·8 (per 100,000 persons) in 2019 to 144·1 in 2020 and 148·3 in 2021. Adults aged 25-44 years had the most pronounced rise in mortality. Widened racial/ethnic disparity was observed, with Hispanics demonstrating the highest excess deaths (67·5%; 95% CI 60·9-74·7%), almost three times that of non-Hispanic whites (23·9%; 95% CI 21·2-26·7%).InterpretationThe United States saw an increase in DM-related mortality during the pandemic. The disproportionate rise in young adults and the widened racial/ethnic disparity warrant urgent preventative interventions from diverse stakeholders.FundingNational Natural Science Foundation of China.

Circulating microRNA expression profiles to identify a potential link between prostate cancer and obesity

Effective diagnostic methods are needed to apply appropriate treatment strategies in patients with aggressive prostate cancer. From this point of view, risk factors that cause prostate cancer or its aggressiveness should be considered. Obesity is a critical risk factor for triggering prostate cancer's metastatic properties. microRNAs are used as biomarkers in diagnosing cancer and obesity depending on their tissue-specific expression patterns. This study investigates the role of obesity in the metastatic profile of prostate cancer depending on the differential expression signatures of selected miRNAs in prostate cancer and obese patients. The roles of miR-100, miR-141 and miR-145 in prostate cancer and obesity are partially known. However, their potential to become circular biomarkers in the blood is not elucidated. There is no previous data on miR-4463 and miR-653 on prostate cancer and obesity association. In this study, the blood samples were taken and obtained serum from 69 patients of 6 subgroups that consisted of one healthy group and five unhealthy groups based on their different prostate cancer or obesity levels. Five selected miRNA expression analyses (miR-100, miR-141, miR-145, miR-4463, and miR-653) were performed through total RNA isolation, which was confirmed via synthetic cel-miR-39 miRNA. Quantitative Real-Time PCR analyzed the expression levels of selected miRNAs. Data analysis was performed via normalising target miRNA expression levels with cel-miR-39. In this study, we found that the relationship between prostate cancer and obesity was investigated at the molecular level. It was suggested that target miR-100 could be a promising biomarker for non-obese and aggressive prostate cancer patients. miR-145 is a more potential biomarker than miR-141 for non-aggressive and non-obese patients. miR-4463 can be used to predict more prostate cancer patients than obese patients. Lastly, miR-653 can be a biomarker for non-aggressive prostate cancer cells.

Seropositivity of Anti-Toxoplasma gondii Antibodies in Owners and Their Dogs Living on Island and Mainland Seashore Areas of Southern Brazil.

Although toxoplasmosis has been considered among the most neglected zoonoses worldwide, no study has focused on the frequency and associated risk factors of owners and their dogs living on an island and mainland seashore areas. Accordingly, anti-Toxoplasma gondii IgG antibodies were screened by indirect fluorescent antibody test (IFAT) in owners and dogs from three oceanic islands and two nearby mainland harbor areas, with associated risk factors for toxoplasmosis assessed by univariable and multivariable logistic regression models. Overall, anti-T. gondii seropositivity was observed in 59/328 (18.0%) owners and 66/283 (23.3%) dogs, with no statistical difference between owners (p = 0.360) and dogs (p = 0.655) from islands and mainland areas. Consumption of local water springs (p = 0.016; OR = 2.11) was an associated risk factor for T. gondii seropositivity, and owners with the habit of spring water intake were twice more likely seropositive (p = 0.014; OR = 2.14). Presence of anti-T. gondii antibodies in dogs was associated with seropositive owners (p = 0.008; OR = 2.81), household consumption of beef meat (p = 0.042; OR = 1.7) and chicken (p = 0.026; OR = 2.9). Despite being lower than the worldwide prevalence, toxoplasmosis seropositivity in owners and their dogs in southern Brazil was influenced by the positive owner, water source, and meat consumption, and not by inhabiting islands or seashore mainland areas, presence of dogs, cats, or both. In addition, drinking water quality should always be considered a critical risk factor for toxoplasmosis on islands.

The Immune System as a Therapeutic Target for Alzheimer's Disease.

Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder and is the most common cause of dementia. Furthermore, aging is considered the most critical risk factor for AD. However, despite the vast amount of research and resources allocated to the understanding and development of AD treatments, setbacks have been more prominent than successes. Recent studies have shown that there is an intricate connection between the immune and central nervous systems, which can be imbalanced and thereby mediate neuroinflammation and AD. Thus, this review examines this connection and how it can be altered with AD. Recent developments in active and passive immunotherapy for AD are also discussed as well as suggestions for improving these therapies moving forward.