The Presence of Diabetes Mellitus or Pre-diabetes Mellitus Increases Mortality from Heart Disease in a Taiwanese Population: A 10-year Follow-Up Study.

BACKGROUND: We evaluated hyperglycemia-associated mortality in the Taiwanese population by conducting a 10-year retrospective cohort study. METHODS: From 2007 to 2017, all participants, regardless of their age or underlying diseases, were identified at a Health Screening Center in Taiwan. Overall, 114,534 participants were included in the analysis. They were classified into three subgroups according to glycemia and smoking status by combining survival for data analysis. RESULTS: The mean follow-up time, age, and body mass index (BMI) were 8.14 ± 2.22 years, 40.95 ± 12.14 years, and 23.24 ± 3.65 kg/m2, respectively. The cumulative death rate increased from 0.9% in the normal fasting blood glucose(FBG) subgroup to approximately 6% in the diabetes FBG subgroup. After adjusting for age, gender, BMI, high-density lipoprotein, triglycerides, waist circumference(WC), and smoking status, the hazard ratio (HR) for all-cause, cancer, and heart disease mortality in the diabetes mellitus(DM) subgroup was 1.560, 1.381, and 1.828, respectively.HR was 0.989 in all-cause, 0.940 in cancer, and 1.326 in heart disease in the pre-DM subgroup. CONCLUSION: Being tested for pre-DM is related to a higher risk of death from heart disease in the Taiwanese population at baseline. Therefore, cardiovascular risk must be actively measured among diabetes patients every visit.

Relationships between Alcohol Use, Musculoskeletal Pain, and Work-Related Burnout.

Background and Objectives: Burnout affects approximately half of all nurses, physicians, and other clinicians. Alcohol use may impair performance in work-related tasks, leading to decreased productivity and morale. The present study's aim was to determine whether a causal relationship existed between alcohol use, work-related burnout (WB), and musculoskeletal pain. Materials and Methods: A total of 1633 members from a hospital affiliated with a medical university in Taichung, Taiwan, completed questionnaires in 2021, where 1615 questionnaires were declared valid. Questionnaires were used to obtain information on basic demographic variables, and the Nordic Musculoskeletal Questionnaire and Copenhagen Burnout Inventory were used. Statistical analyses were performed using SAS Enterprise Guide 6.1 software, and significance was set at p < 0.05. Results: Work experience, being married, parenthood, leisure activities with family and friends, and regular weekly exercise were negatively associated with WB. In addition, overtime work, irregular and regular shift work, the physician and nurse medical profession, chronic disease (heart disease, diabetes, etc.), neck and both shoulders pain (NBSP), both ankles pain (BAP), and alcohol use frequency (AUF) were positively associated with WB. NBSP could explain the residual effect of AUF on WB. AUF was determined to mediate the relationship between NBSP and WB. In addition, NBSP was found to mediate the relationship between AUF and WB. Conclusions: The individuals who used alcohol to cope with NBSP or those with NBSP who often consumed alcohol had worsened WB due to a vicious circle of musculoskeletal pain and alcohol use. Therefore, medical staff should not consider alcohol use as an option to reduce burnout.

Gender- and age-related differences of statin use on incident dementia in patients with rheumatoid arthritis: a Nationwide population-based cohort study.

BACKGROUND: Some observational studies have found a significant association between the use of statin and a reduced risk of dementia. However, the results of these studies are unclear in patients with rheumatoid arthritis (RA). This study is to determine the association between the use of statins and the incidence of dementia according to sex and age-related differences in patients with RA. METHODS: We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003-2016). The primary outcome assessed was the risk of dementia by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was used to estimate the adjusted hazard ratio of new-onset dementia. Subgroup analysis was also conducted. RESULTS: Among the 264,036 eligible patients with RA aged > 40 years, statin users were compared with non-statin users by propensity score matching at a ratio of 1:1 (25,764 in each group). However, no association was found between the use of statins and the risk of new-onset dementia (NOD) in patients with RA (HR: 1.01; 95% CI: 0.97-1.06). The subgroup analysis identified the use of statin as having a protective effect against developing NOD in male and older patients. CONCLUSION: No association was observed between the use of a statin and the risk of NOD in patients with RA, including patients of both genders and aged 40-60 years, but these parameters were affected by gender and age. The decreased risk of NOD in patients with RA was greater among older male patients. Use of a statin in older male (> 60 years) patients with RA may be needed in clinical practice to prevent dementia.

Resveratrol increases stem cell function in the treatment of damaged pancreas.

Pancreatic damage results in insufficient insulin secretion, leading to type 1 diabetes. Stem cell-based therapy has recently shown potential in the treatment of type 1 diabetes. Resveratrol supplementation has demonstrated a beneficial effect in treating diabetes. This study investigates if adipose-derived stem cells (ADSC), preconditioned with resveratrol, show better effects on experimental diabetic animals. Wistar rats were randomly divided into four groups including sham (normal rats), DM (diabetic rats induced by SZT injection), DM+ADSC (DM rats with receiving autologous ADSC transplantation) and DM+R-ADSC (DM rats receiving resveratrol preconditioned ADSC). The experimental results show that SZT induced pancreatic damage (DM group), including reduction of islet size, fibrosis pathway activation, survival signaling suppression, and apoptotic pathway expression, lead to serum glucose elevation. Autologous ADSC (DM+ADSC group) transplantation shows improvement in the above observations in DM rats. Furthermore, ADSC precondition with resveratrol (DM+R-ADSC group) reveals significant improvement in the above pathological observations over both DM and DM+ADSC groups. We found that ADSC precondition with resveratrol increases the survival marker p-Akt expression, leading to enhanced ADSC viability. This study suggests that ADSC precondition with resveratrol shows potential in the treatment of patients with type 1 DM.

Semi-quantification of the minimum detectable difference of imaging quality of gamma camera SPET for four radionuclides via an innovative PMMA phantom with a V-shaped slit: interpretation of a feasibility study.

OBJECTIVE: An indigenous polymethyl metacrylate (PMMA) phantom with a V-shaped slit and a correlated technique for semi-quantifying the minimum detectable difference (MDD) of single photon emission tomography (SPET) via gamma camera scanning are proposed and validated using four radionuclides. MATERIALS AND METHODS: Radio-actinide solutions of gallium-67 (67Ga), technetium-99m (99mTc), iodine-131 (131I) and thallium-201 (201Tl) were diluted to 11c.c. and thoroughly injected into the continuous zig zag slit of the PMMA phantom. Either depth or edge of the slit between two lines of the V-shape was customized from deep or wide to change into shallow or narrow gradually. Thus, the quantified MDD could be easily evaluated, according to the revised Student's t-test evaluation. The revised Student's t-test was calculated by both full width at half maximum (FWHM) and edge width between two adjacent peaks that were acquired from the original data matrix of SPET. The derived MDD was indicated as for radionuclide, depth, width in mm: For 67Ga, 2.9, 2.13, for 99mTc, 2.5, 0.66, for 131I, 4.7, 2.38 and for 201Tl, 3.3, 2.00, respectively. RESULTS: Technetium-99m had the highest and 131I had the lowest MDD among the four radionuclides. Furthermore, two adjacent peaks of 67Ga could be easily identified with fewer counts than for 201Tl (depth, 2.9 vs. 3.3mm), but its MDD was poorer (width: 2.13 vs.2.00mm). The revised Student's t-test analysis proved to be an acceptable technique for the MDD identification. CONCLUSION: The proposed new combination of PMMA phantom with a V-slit and the revised Student's t-test proved to be instrumental in the MDD of SPET optimization analysis.

Stem cells rescue cardiomyopathy induced by P. gingivalis-LPS via miR-181b.

Systemic inflammation induced by bacterial infection is one of several causative agents for cardiovascular disorders in patients with periodontal disease. Experimental results indicate that miRNAs play important roles in systemic inflammation induced by endotoxins. Further evidence states that stem cell based therapy shows potential in the treatment of inflammatory responses induced by sepsis. This study investigates if stem cells show protective effects on cardiomyocyte damage induced by porphyromonas gingivalis-LPS (Pg-LPS) through regulating miRNAs. H9c2 cardiomyoblasts and neonatal rat cardiomyocytes (NRCMs) were damaged using Pg-LPS in this study. Pg-LPS damaged H9c2 or NRCMs were then rescued using adipose-derived stem cells (ADSC). The experimental results reveal that Pg-LPS treatment is capable of inducing TLR4/NFκB axis activation, cell death signaling and IGF1R/PI3 K/Akt axis suppression. miR181b was downregulated in Pg-LPS damaged H9c2/NRCMs. All markers were improved in H9c2/NRCMs cocultured with ADSC. miR181b mimic and inhibitor confirmed that miR181b plays a central role in regulating the cardio protective effect on Pg-LPS damaged H9c2/NRCMs cocultured with ADSC. miR181b acts as potential therapeutic marker in cardiomyopathy induced by Pg-LPS. Transplantation of adipose-derived stem cells show potential in the treatment of cardiomyopathy induced by porphyromonas gingivalis endotoxin via regulation of miR181b.

Tumorous imaginal disc 1 (TID1) inhibits isoproterenol-induced cardiac hypertrophy and apoptosis by regulating c-terminus of hsc70-interacting protein (CHIP) mediated degradation of Gαs.

Dilated cardiomyopathy (DCM) is the most common form of non-ischemic cardiomyopathy. It is characterized by ventricular chamber dilation, and myocyte hypertrophy. Human tumorous imaginal disc 1 (Tid1), a chaperone protein and response to regulate number of signaling molecules in the mitochondria or cytosol. Tid1 also plays a major role in preventing DCM; however, the role of Tid1 in isoproterenol (ISO)-induced cardiac apoptosis and hypertrophy remains unclear. H9c2 cells were pretreated Tid1 before ISO-induced hypertrophy and apoptosis and then evaluated by IHC, TUNEL assay, IFC, Co-IP, and Western blot. From the IHC experiment, we found that Tid1 proteins were increased in tissues from different stages of human myocardial infarction. Using H9c2 cardiomyoblast cells we found that Tid1 was decreased by ISO treatment. However, over-expression of Tid1S suppressed NFATc3, BNP and calcineurin protein expression and inhibited NFATc3 nuclear translocation in ISO induced cardiomyoblast cells. On the other hand, Tid1S over-expression activated survival proteins p-AKTser473 and decreased caspase-3 and cytochrome c expression. We also found that overexpression of Tid1 enhanced CHIP expression, and induced CHIP to ubiquitinate Gαs, resulting in increased Gαs degradation. Our study showed that Gαs is a novel substrate of CHIP, and we also found that the Tid1-CHIP complex plays an essential role in inhibiting ISO induced cardiomyoblast hypertrophy and apoptosis.

Adipose-derived stem cells decrease cardiomyocyte damage induced by porphyromonas gingivalis endotoxin through suppressing hypertrophy, apoptosis, fibrosis, and MAPK markers.

Heart failure is one of the complications related to periodontal disease. In addition to drugs or herbal medicines, stem cell therapy shows potential in the treatment of cardiomyopathy. This study investigates if stem cells exhibit beneficial effects on cardiomyocyte damage induced by porphyromonas gingivalis endotoxin (Pg-LPS). From the experimental results we find that Pg-LPS reduce cardiomyocyte viability via the activation of apoptosis, hypertrophy, fibrosis and MAPK signaling. Pg-LPS damaged cardiomyocytes co-cultured with adipose-derived stem cells (ADSC) increases cardiomyocyte viability through suppressing the pathological markers described above. Further evidence implies that survival marker, IGF1, secreted from ADSC, may play an important role in the Pg-LPS induced protective effect on cardiomyocyte damage.

Suppression of isoproterenol-induced apoptosis in H9c2 cardiomyoblast cells by daidzein through activation of Akt.

Increased serum norepinephrine level is one of pathological processes relating to heart disease (HD). Estrogens are considered as potential therapeutics for the treatment of HD; however, estrogen supplementation shows some side-effects, such as increasing the risk of developing breast, endometrial and ovarian cancers. This study investigated the cardio-protective effects of daidzein (Dai), a selective estrogen receptor modulator (SERM) from soy bean extract, in H9c2 cardiomyoblast cells treated with isoproterenol (ISO), a norepinephrine analog. In this in vitro model, H9c2 cells treated with Dai at different concentrations showed no statistical difference in cell viability. TdT-mediated digoxigenin-dUTP nick-end labeling (TUNEL) data and western blotting results indicated that Dai treated-H9c2 cells recovered from the damage induced by ISO. The recovery effects of Dai on ISO-induced damage were blocked by inhibition of Akt activation through adding Akt inhibitor. On the other hand, the fold changes of phosphorylated Akt (p-Akt)/Akt normalized with the control for con, 0.25, 0.5, 1, 3 and 24 h of treatment were 1, 2, 5, 13, 11 and 10, respectively. In conclusion, Dai ameliorates apoptosis of cardiomyoblasts induced by ISO through Akt signaling pathway.

Evaluation of the occupational X-rays dose of the medical staff in a cardiac catheterization laboratory using an acrylic phantom and semiconductor dosimeter.

OBJECTIVE: The occupational X-rays doses of medical staff in a cardiac catheterization laboratory were evaluated. METHODS: Four customized acrylic phantoms were used to simulate a patient, medical doctor, assistant, and radiologist to evaluate the in-situ X-rays exposure dose using semiconductor dosimeters. The exposure dose was measured under three scenarios that were preset to imply: no shielding, moderate shielding and complete shielding for the medical staff in the laboratory. The doses were applied by changing the dose area product (DAP) from 11,000 to 500,000mGy·cm(2) in 14 increments. RESULTS: The estimated annual occupational doses for doctors, assistants and radiologists in scenarios I, II, and III were: I) 35.03, 7.78, 1.95; II) 1.95, 0.78, 0.06; and III) 0.19, 0.10, 0.05cSv, respectively. The derived linear regression line of the exposure dose with respect to the DAP were extrapolated to obtain the minimum detectable level (MDL) of DAP for triggering the staff dosimeters. Accordingly, the minimum annual dose was estimated as 0.05cSv. Additional shielding provided measurable protection to the staff. The protective clothing used in scenarios II and III can reduce the original dose from scenario I to ∼3% (scenario II) and ∼0.5% (scenario III). The annual occupational dose also changed with the various X-rays energy settings. The annual dose increased to 126% when the preset X-rays energy was changed from 70 to 100kVp. CONCLUSION: The semiconductor dosimeter proved to be an adequate tool for measuring low doses and low dose rates under these circumstances. The dose can be reduce of I) 35.03, 7.78, 1.95; to II) 1.95, 0.78, 0.06 (∼3%); or III) 0.19, 0.10, 0.05 (∼0.5%)cSv, respectively according to different protective scenarios.

NFIL3 suppresses hypoxia-induced apoptotic cell death by targeting the insulin-like growth factor 2 receptor.

The insulin-like growth factor-II/mannose 6-phosphate receptor (IGF2R) over-expression correlates with heart disease progression. The IGF2R is not only an IGF2 clearance receptor, but it also triggers signal transduction, resulting in cardiac hypertrophy, apoptosis and fibrosis. The present study investigated the nuclear factor IL-3 (NFIL3), a transcription factor of the basic leucine zipper superfamily, and its potential pro-survival effects in cardiomyocytes. NFIL3 might play a key role in heart development and act as a survival factor in the heart, but the regulatory mechanisms are still unclear. IGF2 and IGF2R protein expression were highly increased in rat hearts subjected to hemorrhagic shock. IGF2R protein expression was also up-regulated in H9c2 cells exposed to hypoxia. Over-expression of NFIL3 in H9c2 cardiomyoblast cells inhibited the induction of hypoxia-induced apoptosis and down-regulated IGF2R expression levels. Gel shift assay, double-stranded DNA pull-down assay and chromatin immune-precipitation analyses indicated that NFIL3 binds directly to the IGF2R promoter region. Using a luciferase assay, we further observed NFIL3 repress IGF2R gene promoter activity. Our results demonstrate that NFIL3 is an important negative transcription factor, which through binding to the promoter of IGF2R, suppresses the apoptosis induced by IGF2R signaling in H9c2 cardiomyoblast cells under hypoxic conditions.

Hepatoprotective Effects of Traditional Chinese Medicine on Liver Fibrosis from Ethanol Administration following Partial Hepatectomy.

The aim of this study was to establish the effective hepatoprotective properties of traditional Chinese medicines (TCMs) in fibrotic rat liver regeneration after partial hepatectomy (PHx). Fibrosis was induced in rats by ethanol (EtOH, 5 ml/kg) administration for 6, 24, 72, and 168 h. The rats were then fed four TCMs (1 g/kg/day, Codonopsis pilosula (CP), Salvia miltorrhiza Bunge (SMB), Bupleurum kasi (BK), and Elephantopus scaber L (ESL)) to Spraque-Dawley rats for 6, 24, 72 and 168 h, respectively. Surgical 70% cirrhotic fibrosis PHx was then conducted at 6, 24, 72, and 168 h. The effects on liver regeneration were examined to estimate and measure hepatocyte growth factor (HGF), focal adhesion kinase (FAK), Cyclin D1, Cyclin E, and retinoblastoma protein (pRb) protein expression using Western blotting analysis. Cyclin D1, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and TIMP-3 mRNA by Reverse transcription polymerase chain reaction (RT-PCR) were analyzed in cirrhotic fibrosis rats. Transforming growth factor-ß1 (TGF-ß1), Cyclin D1, Cyclin E, pRb and E2F mRNA expression levels were determined in fibrotic rats following PHx using RT-PCR. We found elevated glutamyl oxaloacetic transaminase (GOT), glutamyl pyrubic transaminase (GPT), alkaline phosphatase (ALP), gammaglutamyl transpeptidase (γ-GT), glutathione (GSH), nonprotein sulfhydryl (NPSH) and total bilirubin in serum after 6 h EtOH administration. These levels were progressively decreased over 168 h. Total protein and albumin were reduced in serum after 6 h administration and then progressively increased. In contrast, tissues disorder histology and morphology were determined in liver sections. After rats were fed TCMs we found that SMB extraction not only induced HGF, FAK, Cyclin D1, and pRb protein expression and Cyclin D1 mRNA increases, but also reduced MMP-2 and MMP-9 after 24 and 72 h post injury. In the cell cycle S phase the Cyclin E protein expression was increased by ESL. CP induced TIMP-1, TIMP-2 and TIMP-3 mRNA increases in fibrotic rats. We detected liver regeneration in fibrotic rats. We also found that the liver regeneration index increased from 6 to 168 h post PHx. After 168 h fibrotic liver regeneration rats exhibited reduced TGF-ß1 mRNA expression and enhanced Cyclin D1, Cyclin E, pRb and E2F mRNA expression. TCMs play a crucial role in the early mediating process in fibrotic rat liver regeneration after PHx.

CREB Negatively Regulates IGF2R Gene Expression and Downstream Pathways to Inhibit Hypoxia-Induced H9c2 Cardiomyoblast Cell Death.

During hypoxia, gene expression is altered by various transcription factors. Insulin-like growth factor-II (IGF2) is known to be induced by hypoxia, which binds to IGF2 receptor IGF2R that acts like a G protein-coupled receptor, might cause pathological hypertrophy or activation of the mitochondria-mediated apoptosis pathway. Cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB) is central to second messenger-regulated transcription and plays a critical role in the cardiomyocyte survival pathway. In this study, we found that IGF2R level was enhanced in H9c2 cardiomyoblasts exposed to hypoxia in a time-dependent manner but was down-regulated by CREB expression. The over-expression of CREB in H9c2 cardiomyoblasts suppressed the induction of hypoxia-induced IGF2R expression levels and reduced cell apoptosis. Gel shift assay results further indicated that CREB binds to the promoter sequence of IGF2R. With a luciferase assay method, we further observed that CREB represses IGF2R promoter activity. These results suggest that CREB plays an important role in the inhibition of IGF2R expression by binding to the IGF2R promoter and further suppresses H9c2 cardiomyoblast cell apoptosis induced by IGF2R signaling under hypoxic conditions.

Risk of New-onset Stroke in Patients with Type 2 Diabetes with Chronic Kidney Disease on Sodium-glucose Co-transporter-2 Inhibitor Users.

Clinical studies have investigated the effects of using sodium-glucose co-transporter-2 (SGLT2) inhibitors on the development of new-onset stroke (NOS) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), but the findings are inconsistent. This study aimed to examine the association between the use of SGLT2 inhibitors and NOS risk in patients with T2D and CKD. We conducted a nationwide retrospective cohort study using data from the Taiwan Health Insurance Review and Assessment Service database for the years 2004 to 2019. The primary outcome was the risk of incident stroke, which was estimated using hazard ratios (HRs) and 95% confidence intervals (CIs). We used multiple Cox regression modeling to analyze the association between SGLT2 inhibitor use and the risk of stroke in patients with T2D and CKD. In a cohort of 113,710 patients with T2D and CKD who were using SGLT2 inhibitors and 227,420 patients with T2D and CKD who were not using SGLT2 inhibitors, after applying a 1:2 sex- and age-matching strategy, 2,842 and 7,169 NOS events were recorded, respectively. The event rate per 10,000 person-months was 10.60 (95% CI 10.21 to 11.03) for SGLT2 inhibitor users and 13.71 (13.39-14.03) for non-SGLT2 inhibitor users. After adjusting for the index year, sex, age, comorbidities, and concurrent medication, there was a decreased risk of NOS for SGLT2 inhibitor users (adjusted HR 0.80; 95% CI 0.77-0.84) compared with non-SGLT2 inhibitor users. The sensitivity test for the propensity score 1:1-matched analyses showed similar results (adjusted HR 0.80; 95% CI 0.76-0.84). The type of SGLT2 inhibitor subgroup analysis for incident stroke showed consistent results. We concluded that the use of SGLT2 inhibitors in patients with T2D and CKD was associated with significantly low rates of NOS. The significantly low rates of NOS in patients with T2D and CKD were greater among females and less than 50 years patients.

Risk of New-Onset Dementia in Patients with Chronic Kidney Disease on Statin Users: A Population-Based Cohort Study.

Patients with chronic kidney disease (CKD) are at a higher risk for developing dementia than the general population. Clinical studies have investigated the effects of statin use on new-onset dementia (NOD) in patients with CKD; however, the findings are inconsistent. This study examines the association between the use of statins and NOD in patients with CKD. We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003-2016). The primary outcome assessed the risk of incident dementia by estimating the hazard ratios and 95% confidence intervals. Therefore, multiple Cox regression models were conducted to analyse the association between statin use and NOD in patients with CKD. There were 24,090 participants with statin use and 28,049 participants without statin use in patients with new-diagnosed CKD; the NOD event was 1390 and 1608, respectively. There was a trend of reduction association between statin users and NOD events after adjusted sex, age, comorbidities, and concurrent medication (adjusted HR 0.93, 95% CI 0.87 to 1.00) in the 14 years of the follow-up. Sensitivity test for the propensity score 1:1 matched analyses showed similar results (adjusted HR 0.91, 95% CI 0.81 to 1.02). The subgroup analysis also identified the use of statins as having a trend against developing NOD in patients with hypertension. In conclusion, statin therapy may effectively reduce the risk of NOD in patients with CKD. More studies are needed to credibly evaluate the effects of statin therapy on the prevention of NOD in patients with CKD.

Potential risk quantification from multiple biological factors via the inverse problem algorithm as an artificial intelligence tool in clinical diagnosis.

BACKGROUND: The inverse problem algorithm (IPA) uses mathematical calculations to estimate the expectation value of a specific index according to patient risk factor groups. The contributions of particular risk factors or their cross-interactions can be evaluated and ranked by their importance. OBJECTIVE: This paper quantified the potential risks from multiple biological factors by integrated case studies in clinical diagnosis via the IPA technique. Acting as artificial intelligence field component, this technique constructs a quantified expectation value from multiple patients' biological index series, e.g., the optimal trigger timing for CTA, a particular drug in blood concentration data, the risk for patients with clinical syndromes. METHODS: Common biological indices such as age, body surface area, mean artery pressure, and others are treated as risk factors upon their normalization to the range from -1.0 to +1.0, with a non-dimensional zero point 0.0 corresponding to the average risk factor index. The patients' quantified indices are re-arranged into a large data matrix. Next, the inverse and column matrices of the compromised numerical solution are constructed. RESULTS: This paper discusses quasi-Newton and Rosenbrock analyses performed via the STATISTICA program to solve the above inverse problem, yielding the specific expectation value in the form of a multiple-term nonlinear semi-empirical equation. The extensive background, including six previous publications of these authors' team on IPA, was comprehensively re-addressed and scrutinized, focusing on limitations, stumbling blocks, and validity range of the IPA approach as applied to various tasks of preventive medicine. Other key contributions of this study are detailed estimations of the effect of risk factors' coupling/cross-interactions on the IPA computations and the convergence rate of the derived semi-empirical equation viz. the final constant term. CONCLUSION: The main findings and practical recommendations are considered useful for preventive medicine tasks concerning potential risks of patients with various clinical syndromes.

Exposure to Proton Pump Inhibitors and the Risk of Incident Asthma in Patients with Coronary Artery Diseases: A Population-Based Cohort Study.

We aimed to determine the association between proton pump inhibitor (PPI) use and incident asthma in patients with coronary artery disease (CAD). This nationwide cohort study collected claims data from the Taiwanese Bureau of National Health Insurance from 2004 to 2013. The primary outcome, i.e., the risk of incident asthma, was assessed by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). The adjusted HR of asthma development was estimated using the Cox regression model. Sensitivity and subgroup analyses were also conducted. A total of 8894 PPI users and 12,684 H2-receptor antagonist (H2RA) users were included in patients with CAD. Compared with H2RA use, an increased risk of incident asthma was found between PPI use and the risk of incident asthma in patients with CAD after adjusting for sex, age, urbanization, and low income (HR: 1.41; 95% CI: 1.04-1.89). The sensitivity analysis results were consistent with the main analysis results. However, the subgroup analysis revealed no association of incident asthma in patients with diabetes mellitus, hyperlipidemia, stroke, allergic rhinitis, pneumonia, cancer, or depression in the PPI group compared with those in the H2RA group. In conclusion, PPI use increased the risk of asthma development in patients with CAD.