Abstract Background and purpose Intravenous Thrombolysis (IVT) prior to Mechanical Thrombectomy (MT) for Acute Ischaemic Stroke (AIS) due to Large-Vessel Occlusion (LVO) remains controversial. Therefore, the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy (BT) compared with direct MT in patients with AIS due to LVO. Methods Four databases were searched until 01 February 2023. Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included. Odds Ratios (ORs) and 95 % Confidence Intervals (CIs) for efficacy and safety outcomes were pooled using a random-effects model. Results Of the 12 studies, 86,695 patients were included. In patients with AIS due to LVO, BT group was associated with higher odds of achieving excellent functional outcome (modified Rankin Scale score 0-1) at 90 days (OR = 1.48, 95 % CI 1.25-1.75), favorable discharge disposition (to the home with or without services) (OR = 1.33, 95 % CI 1.29-1.38), and decreased mortality at 90 days (OR = 0.62, 95 % CI 0.56-0.70), as compared with the direct MT group. In addition, the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group. Conclusion The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO. These findings support the current practice in a real-world setting and strengthen their validity. For patients eligible for both IVT and MT, BT remains the standard treatment until more data are available. (IVT (MT (AIS LargeVessel Large Vessel LVO (LVO controversial Therefore metaanalysis meta analysis realworld real world (BT 0 2023 included ORs (ORs 9 CIs (CIs randomeffects random effects model 1 86695 86 695 86,69 modified 0-1 OR 148 48 1.48 1.251.75, 125175 1.25 1.75 , 25 75 1.25-1.75) services 133 33 1.33 1.291.38, 129138 1.29 1.38 29 38 1.29-1.38) 062 62 0.62 0.560.70, 056070 0.56 0.70 56 70 0.56-0.70) addition validity 202 8669 8 69 86,6 0- 14 4 1.4 251 1.251.75 12517 125 1.2 175 1.7 2 7 1.25-1.75 13 3 1.3 291 1.291.38 12913 129 138 1.29-1.38 06 6 0.6 560 0.560.70 05607 056 0.5 070 0.7 5 0.56-0.70 20 866 86, 1. 1.251.7 1251 17 1.25-1.7 1.291.3 1291 1.29-1.3 0. 0.560.7 0560 05 07 0.56-0.7 1.251. 1.25-1. 1.291. 1.29-1. 0.560. 0.56-0. 1.251 1.25-1 1.291 1.29-1 0.560 0.56-0 1.25- 1.29- 0.56-

ABSTRACT The objective of this study was to analyze data on physical activity and rumination time monitored via collars at the farm coupled with milk yield recorded by the rotary milking system to predict cows based on several disorders using the binary Logistic regression conducted with R software. Data for metritis (n=60), mastitis (n=98), lameness (n=35), and digestive disorders (n=52) were collected from 1,618 healthy cows used to construct the prediction model. To verify the feasibility and adaptability of the proposed method, we analyzed data of cows in the same herd (herd 1) not used to construct the model, and cows in another herd (herd 2) with data recorded by the same type of automated system, and led to detection of 75.0%, 64.2%, 74.2%, and 76.9% animals in herd 1 correctly predicted to suffer from metritis, mastitis, lameness, and digestive disorders, respectively. For cows in herd 2, 66.6%, 58.8%, 80.7%, and 71.4% were correctly predicted for metritis, mastitis, lameness, and digestive disorders, respectively. Compared with traditional clinical diagnoses by farm personnel, the algorithm developed allowed for earlier prediction of cows with a disorder. software n=60, n60 n n=60 , 60 (n=60) n=98, n98 n=98 98 (n=98) n=35, n35 n=35 35 (n=35) n=52 n52 52 (n=52 1618 618 1,61 model method 2 750 75 0 75.0% 642 64 64.2% 742 74 74.2% 769 76 9 76.9 respectively 666 66 6 66.6% 588 58 8 58.8% 807 80 7 80.7% 714 71 4 71.4 personnel disorder n6 n=6 (n=60 n9 n=9 (n=98 n3 n=3 3 (n=35 n=5 n5 5 (n=5 161 61 1,6 75.0 64.2 74.2 76. 66.6 58.8 80.7 71. n= (n=6 (n=9 (n=3 (n= 16 1, 75. 64. 74. 66. 58. 80. (n

RESUMO Os objetivos deste estudo foram analisar dados sobre a atividade física e o tempo de ruminação monitorados através de coleiras na fazenda junto com a produção de leite registrada pelo sistema rotativo de ordenha para prever vacas com base em vários distúrbios utilizando o software de regressão logística binária realizado com o software R. Dados para metrite (n=60), mastite (n=98), manqueira (n=35) e distúrbios digestivos (n=52) foram coletados de 1.618 vacas saudáveis foram usados para construir o modelo de previsão. Para verificar a viabilidade e adaptabilidade do método proposto, analisamos os dados de vacas do mesmo rebanho (rebanho 1) não utilizadas para construir o modelo, e vacas de outro rebanho (rebanho 2) com dados registrados pelo mesmo tipo de sistema automatizado, e levamos à detecção de 75,0%, 64,2%, 74,2%, e 76,9% de animais do rebanho 1 previstos corretamente para sofrer de metrite, mastite, manqueira e distúrbios digestivos, respectivamente. Para as vacas do rebanho 2, 66,6%, 58,8%, 80,7% e 71,4% foram previstos corretamente para metrite, mastite, manqueira e distúrbios digestivos, respectivamente. Em comparação com os diagnósticos clínicos tradicionais feitos pelo pessoal da fazenda, o algoritmo desenvolvido permitiu a previsão antecipada de vacas com um distúrbio. R n=60, n60 n n=60 , 60 (n=60) n=98, n98 n=98 98 (n=98) n=35 n35 35 (n=35 n=52 n52 52 (n=52 1618 618 1.61 proposto 2 automatizado 750 75 0 75,0% 642 64 64,2% 742 74 74,2% 769 76 9 76,9 respectivamente 666 66 6 66,6% 588 58 8 58,8% 807 80 7 80,7 714 71 4 71,4 distúrbio n6 n=6 (n=60 n9 n=9 (n=98 n=3 n3 3 (n=3 n=5 n5 5 (n=5 161 61 1.6 75,0 64,2 74,2 76, 66,6 58,8 80, 71, n= (n=6 (n=9 (n= 16 1. 75, 64, 74, 66, 58, (n

Abstract In order to develop a quick method for predicting fatty acid in rice storage, gas chromatography-ion mobility spectrometry (GC-IMS) was applied to detect and analyze volatile organic compounds (VOCs) at different rice storage stages, and partial least squares regression (PLSR) algorithm was used to establish a linear regression model between fatty acid values and characteristic VOCs. The results showed that rice fatty acid values increased gradually with extension of storage time. Odor components of rice mainly included alcohols and aldehydes. Except for 1-octene-3-alcohol, the content of other VOCs showed an overall downward trend during the storage period. After variable optimization using two different algorithms, the correlation coefficient of the PLSR cross validation model could reach 0.9544, and the corresponding root mean square error was 2.4093. In conclusion, fatty acid values of rice with different storage periods could be accurately predicted by using characteristic VOCs variables and chemometric tools, which would provide a rapid and nondestructive detection method for rice quality during storage based on odor information.

Abstract Background Duchenne muscular dystrophy (DMD) is an X-linked lethal genetic disorder for which there is no effective treatment. Previous studies have shown that stem cell transplantation into mdx mice can promote muscle regeneration and improve muscle function, however, the specific molecular mechanisms remain unclear. DMD suffers varying degrees of hypoxic damage during disease progression. This study aimed to investigate whether induced pluripotent stem cells (iPSCs) have protective effects against hypoxia-induced skeletal muscle injury. Results In this study, we co-cultured iPSCs with C2C12 myoblasts using a Transwell nested system and placed them in a DG250 anaerobic workstation for oxygen deprivation for 24 h. We found that iPSCs reduced the levels of lactate dehydrogenase and reactive oxygen species and downregulated the mRNA and protein levels of BAX/BCL2 and LC3II/ LC3I in hypoxia-induced C2C12 myoblasts. Meanwhile, iPSCs decreased the mRNA and protein levels of atrogin-1 and MuRF-1 and increased myotube width. Furthermore, iPSCs downregulated the phosphorylation of AMPKA and ULK1 in C2C12 myotubes exposed to hypoxic damage. Conclusions Our study showed that iPSCs enhanced the resistance of C2C12 myoblasts to hypoxia and inhibited apoptosis and autophagy in the presence of oxidative stress. Further, iPSCs improved hypoxia-induced autophagy and atrophy of C2C12 myotubes through the AMPK/ULK1 pathway. This study may provide a new theoretical basis for the treatment of muscular dystrophy in stem cells.

Abstract To observe the influence of thalidomide on tumor necrosis factor-a (TNF-α) of spontaneous type-2 diabetes rat (kk-Ay rat) model, and to explore the clinical value of TNF-a mediated inflammation approach to improve the injury on epithelial cell of kidney tubules. There are 30 kk-Ay rates being chosen to establish the Diabetic Nephropathy model and divided into thalidomide group and the model control group, 15 pieces for each group respectively. The levels of TNF-α, IL-1β, interleukin -6 (IL-6) and interleukin -18 (IL-18) of kk-Ay in the thalidomide group and the model control group were both at a higher level before treatment, but the difference was not statistically significant (P >0.05); The levels of TNF-α, IL-1β, interleukin -6 (IL-6) and interleukin -18 (IL-18) in kk-Ay rats 8/10/12 weeks after the treatment in the thalidomide group were significantly decreased, with statistically significant differences compared with the model control group (P < 0.05). The histopathological changes of kidney tubules epithelial cell injury on rats were observed through dissection. Thalidomide will effectively lower TNF-α and IL-1β expression levels in kk-Ay rat models, reduce inflammatory response, and thus improve damage on kidney tubules epithelial cell, which is worthy of further exploration and application.

Abstract The paper aimed to investigate the effects of up-regulation and down-regulation of Mir-299-3p on the proliferation, migration, invasion and apoptosis of lung adenocarcinoma cell line H1299, and to preliminarily explore the mechanism of Mir-299-3p regulating the biological behavior of lung adenocarcinoma cells. Mir-299-3p inhibitor and Mir-299-3p mimics were transfected into lung adenocarcinoma cell line H1299, and the transfection efficiency was measured by fluorescence microscopy. The successfully transfected lung adenocarcinoma cells were detected of proliferation, migration, invasion, and apoptosis. Mir-299-3p inhibitor and Mir-299-3p mimics were used to down-regulate and up-regulate Mir-299-3p respectively. Western blot was employed to detect the expressions of STAT3, p-STAT3, caspase3, Bcl-2, Bax and MMP-9 proteins in lung adenocarcinoma cells. Small interfering RNA technology was applied to construct a cell line with low expression of PTPRD. WB was used to measure the transfection efficiency to determine whether the down-regulation of PTPRD can partially or completely reverse the proliferation, migration, invasion, and apoptosis of lung adenocarcinoma cells after the down-regulation of Mir-299-3p. It was also determined whether the down-regulation of PTPRD can partially or completely reverse the effect of Mir-299-3p down-regulation on the expressions of p-STAT3, MMP-9, Cleaved-caspase3, Bcl-2 and Bax proteins in lung adenocarcinoma cells. Down-regulation of Mir-299-3p can inhibit the proliferation and invasion of lung adenocarcinoma cell H1299, promote cell apoptosis, inhibit the expression of p-STAT3 and MMP-9, promote the expressions of apoptosis-inducing proteins such as Bax and Cleaved-caspase3, and also inhibit the expression of apoptosis inhibitor protein Bcl-2. The up-regulation of Mir-299-3p worked in the opposite way. PTPRD is the direct target gene of Mir-299-3p. Mir-299-3p may directly target PTPRD to regulate the expressions of p-STAT3, MMP-9, Cleaved-caspase3, Bcl-2 and Bax proteins to affect the biological behavior of lung adenocarcinoma cells.

Abstract On the increasing prevalence of using mAbs (monoclonal antibodies) in cancer therapy and the severe risk of hyperglycemia, we aimed to analyze the main clinical ADRs of mAbs, with a focus on adverse hyperglycemic events associated with currently clinically used mAbs. mAbs as well as target information were selected from Martinadale book and published articles. Drug approving information was collected from each government website, and ADR statistic data were collected from VigibaseR, comparing with Adverse Event Reporting System of US FDA. Top 10 mAbs were classified within listing in total ADR records, ADRs per year, hyperglycemic ADR records. Vigibase data were updated onto 15 Feb 2019. 20 mAbs were analyzed with 263217 ADR reports, wherein 16751 records on Metabolism and nutrition disorders and 1444 records on Glucose metabolism disorders. The geographic, age, gender distributions and annual ADR report numbers were listed respectively. Of the top 10, Rituximab, Bevacizumab and Nivolumab were on the top 3 in total ADR record and hyperglycemic record. Top 3 record results were similar in Vigibase and FDA database. It is of increasing importance for clinicians to be aware of early detection, patient management, or drug selection strategies when using mAbs, particularly within the high glycemic risk-reported mAbs, to improve the efficacy and tolerability of mAbs regiment and optimize patient outcomes.

Abstract Background: Metastatic melanoma has a high mortality rate and poor survival. This is associated with efficient metastatic colonization, but the underlying mechanisms remain elusive. Communication between cancer stem cells (CSCs) and cancer cells plays an important role in metastatic dissemination. Whether cancer stem cells can alter the metastatic properties of non-CSC cells; and whether exosomal crosstalk can mediate such interaction, have not been demonstrated in melanoma prior to this report. Results: The results revealed that exosomes secreted by highly metastatic melanoma CSCs (OL-SCs) promoted the invasiveness of the low metastatic melanoma cells (OL) and accelerated metastatic progression. miR-1268a was up-regulated in cells and exosomes of OL-SCs. Moreover, OL-SCs-derived exosomal miR-1268a, upon taking up by OL cells, promoted the metastatic colonization ability of OL cells in vitro and in vivo. In addition, the pro-metastatic activity of exosomal miR-1268a is achieved through inhibition of autophagy. Conclusion: Our study demonstrates that OL cells can acquire the “metastatic ability” from OL-SCs cells. OL-SCs cells achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-1268a, to the targeted OL cells which in turn augments metastatic colonization by inactivating the autophagy pathway in OL cells.

Resumo Introdução: A fístula congênita do seio piriforme é uma doença relativamente rara na prática clínica; a maioria se manifesta na infância; entretanto, os médicos geralmente têm conhecimento insuficiente sobre essa condição clínica e seu diagnóstico é facilmente feito de forma errônea. Objetivo: Identificar as características do abscesso cervical profundo devido à fístula congênita de seio piriforme em crianças. Método: Estudo retrospectivo de 21 casos de janeiro de 2016 a agosto de 2018 em nosso hospital. Idade de início, características clínicas, exames auxiliares e tratamento clínico dos pacientes foram resumidos para analisar o diagnóstico, as características do tratamento e o prognóstico. Resultados: Foram incluídas crianças de 11 dias a 12 anos, com média de 3,5 anos. Vinte pacientes tinham fístula congênita de seio piriforme no lado esquerdo e um no lado direito; a tomografia computadorizada cervical com contraste mostrava distribuição líquido-gasosa ou sombra aérea nos abscessos em 18 casos. O ultrassom cervical demonstrou eco gasoso na região da tireoide em 10 casos. Todos os pacientes foram submetidos a plasma de baixa temperatura para queimar a fístula interna e retornaram ao hospital para exame com laringoscópio eletrônico e ultrassonografia cervical aos 3 meses, 6 meses e um ano após a cirurgia. Não houve recorrências. Conclusão: A fístula congênita de seio piriforme é uma causa importante de abscesso cervical profundo em crianças. A presença de conteúdo líquido-gasoso purulento ou sombra gasosa na tomografia computadorizada ou no ultrassom cervical sugere uma alta possibilidade da presença de uma fístula interna e a ablação endoscópica a baixa temperatura pode ser feita ao mesmo tempo que a endoscopia diagnóstica.

Abstract Introduction: Congenital piriform sinus fistula is a relatively rare type of disease in clinical practice, most occurring during childhood, but doctors have insufficient knowledge regarding this disease, easily misdiagnosing it. Objectives: This study aimed to identify the characteristics of deep neck abscess due to congenital piriform sinus fistula in children. Methods: We performed a retrospective study of 21 cases from January 2016 to August 2018 in our hospital. The onset age, clinical characteristics, auxiliary examination and clinical treatment of the patients was summarized to analyze the diagnosis, treatment characteristics and prognosis. Results: Children from 11 days to 12 years-old were enrolled, with an average age of 3.5 years. Twenty patients had left congenital piriform sinus fistula and 1 had right congenital piriform sinus fistula. Cervical enhanced computed tomography imaging showed gas-liquid equilibrium or air-shadow in the abscesses in 18 cases, and neck ultrasound demonstrated gas echo in the thyroid region in 10 cases. All patients underwent low temperature plasma to seal the internal fistula and returned to the hospital for electronic laryngoscope and neck ultrasound examination at 3 months, 6 months and 1 year after the surgery. No recurrence occurred in any patient. Conclusion: Congenital piriform sinus fistula is an important cause of deep neck abscess in children. The presence of purulent gas-liquid equilibrium or air shadow in cervical-enhanced computed tomography or ultrasound suggests a high possibility of the presence of an internal fistula, and endoscopic low temperature ablation can be done at the same time as the diagnostic endoscopy.

Abstract Objective: To evaluate the efficacy of hybrid transthoracic periventricular device closure of ventricular septal defects (VSDs) in a single center. Methods: All patients who underwent hybrid transthoracic periventricular device closure of VSDs between January 2018 and December 2019 were retrospectively analyzed. The preoperative, operative and postoperative findings and clinical follow-ups were reviewed. Results: A total of 59 patients underwent the procedure. Transesophageal echocardiographic guidance was used in all procedures. The procedure was successful in 57 procedures (97%). The procedures of two patients were changed to open-heart surgery during the same intervention due to severe aortic insufficiency (the device was not deployed) and significant residual shunt after device deployment. One major complication (1.7%) was observed after the procedure. The patient’s device was dislodged within 12 hours after the procedure, and this patient underwent device extraction and VSD patch closure due to significant residual shunt. Eight (14%) minor complications were observed after the procedure, and three of them persisted during follow-up. Three of these eight complications were incomplete right bundle branch block, one of which resolved during follow-up; two were mild residual shunts, one of which resolved during follow-up; two were mild new-onset tricuspid valve insufficiencies; and one was mild new-onset mitral valve insufficiency; all valvular insufficiencies were resolved during follow-up. Conclusions: Hybrid transthoracic periventricular device closure of VSD seems to be a good alternative approach due to its procedural success and low risk rates. The best advantage of the procedure is the possibility of switching to open-heart surgery, if necessary. Objective (VSDs center Methods 201 analyzed preoperative followups follow ups reviewed Results 5 97%. 97 97% . (97%) openheart open heart deployed deployment 1.7% 17 1 7 (1.7% s 14% 14 (14% followup. followup up. up follow-up block shunts newonset new onset Conclusions rates necessary 20 9 (97% 1.7 (1.7 (14 2 (97 1. (1. (1 (9 (

Abstract Cassava (Manihot esculenta Crantz) is worldwide the sixth-largest food crop and highly drought resistant. The expression of the myeloblastosis (MYB) family protein MeMYB26 in cassava was previously reported to be significantly up-regulated under water deficit. To study the basic characterization, natural variations and potential functions of MeMYB26 for drought resistance in cassava, the protein was subjected to bioinformatics analysis, multiplex-PCR with next-generation sequencing and candidate association studies. The results indicated that MeMYB26 is a typical transcription factor, with two MYB DNA-binding and transcriptional activation domains. One stop-gained and five nonsynonymous variations in the genomic region of MeMYB26 were significantly associated with drought resistance traits. The results of the scale-free coexpression network showed that the MeMYB26 gene plays a critical role in plant stress resistance, growth and biomass development. It was concluded that MeMYB26 is a reliable candidate gene associated with drought tolerance and biomass storage in cassava.

Abstract Background Snake venoms are complex mixtures of toxic proteins or peptides encoded by various gene families that function synergistically to incapacitate prey. In the present study, in order to unravel the proteomic repertoire of Deinagkistrodon acutus venom, some trace abundance components were analyzed. Methods Shotgun proteomic approach combined with shotgun nano-LC-ESI-MS/MS were employed to characterize the medically important D. acutus venom, after collected samples were enriched with the combinatorial peptide ligand library (CPLL). Results This avenue helped us find some trace components, undetected before, in D. acutus venom. The results indicated that D. acutus venom comprised 84 distinct proteins from 10 toxin families and 12 other proteins. These results are more than twice the number of venom components obtained from previous studies, which were only 29 distinct proteins obtained through RP-HPLC for the venom of the same species. The present results indicated that in D. acutus venom, the most abundant components (66.9%) included metalloproteinases, serine proteinases, and C-type lectin proteins; the medium abundant components (13%) comprised phospholipases A2 (PLA2) and 5’-nucleotidases and nucleases; whereas least abundant components (6%) were aminopeptidases, L-amino acid oxidases (LAAO), neurotoxins and disintegrins; and the trace components. The last were undetected before the use of conventional shotgun proteomics combined with shotgun nano-LC-ESI-MS/MS, such as cysteine-rich secretory proteins Da-CRPa, phospholipases B-like 1, phospholipases B (PLB), nerve growth factors (NGF), glutaminyl-peptide cyclortransferases (QC), and vascular non-inflammatory molecules 2 (VNN2). Conclusion These findings demonstrated that the CPLL enrichment method worked well in finding the trace toxin proteins in D. acutus venom, in contrast with the previous venomic characterization of D. acutus by conventional LC-MS/MS. In conclusion, this approach combined with the CPLL enrichment was effective for allowing us to explore the hidden D. acutus venomic profile and extended the list of potential venom toxins.

ABSTRACT Objective This study aimed to present the impact of age and gender on thyroid hormone levels in a large Chinese population with sufficient iodine intake. Subjects and methods A total of 83643 individuals were included and were stratified by age and gender. The median, 2.5th and 97.5th of thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and FT3/FT4 ratio were calculated for both genders for every decade from 18 to over 80 years. TSH, FT3, FT4, FT3/FT4 distribution in each age group was evaluated for females and males using smoothing splines in the generalized additive models (GAM). TSH concentrations were compared in the different age groups in gender. Results In the over 80s age group, the TSH level (median: 2.57 mIU/L, 2.5th-97.5th: 0.86-7.56 mIU/L) was significantly higher than other age groups, irrespective to gender (P<0.001). Females had a higher TSH value than males in all age groups (P<0.001). Results of the smoothing curves showed that TSH increased with age, FT3 concentration was higher in males than in females and the tendency of the FT3/FT4 ratio was basically similar to that of FT3. TSH concentration in the 50s age group (median 2.48 mIU/L for females versus 2.00 mIU/L for males) was significantly higher than that in the 30s age group (median 2.18 mIU/L for females versus median 1.85 mIU/L for males). Conclusions In accord with increasing TSH values during aging, females and older adults have lower FT3 values and lower FT3/FT4 ratios, while the FT4 values remain stable.

Abstract INTRODUCTION: Leptin (LEP) is a peptide hormone that acts via leptin receptor (LEPR) binding. Genetic evidence from different human populations has implicated LEP/LEPR in the pathogenesis of coronary artery disease (CAD), and suggests that certain LEP/LEPR gene polymorphisms may increase the risk of CAD. The aim of this study was to assess two single nucleotide polymorphisms (SNPs) in LEP genes (rs2167270 and rs7799039) and two in LEPR genes (rs6588147, rs1137100) for association with CAD. METHODS: We enrolled 271 North Chinese Han CAD patients, and 113 healthy age- and sex-matched controls. Genomic DNA was extracted from whole blood, and the four SNPs were assessed using a MassArray system. RESULTS: The G allele frequency at rs2167270 was significantly higher among CAD cases than among controls. The AG genotype at rs7799039 was associated with a significantly decreased risk of CAD unlike the AA genotype used as the reference. The A allele was significantly associated with the CAD patient group. Interestingly, statistically significant differences in genotype and allele frequency at LEP rs2167270 and rs7799039 existed among females but not among males. CONCLUSIONS: The current study detected a significant association between genetic variations at LEP rs7799039 and rs2167270 and the risk of CAD in a north Chinese population, and revealed that LEP rs2167270 and rs7799039 gene polymorphisms might act as predisposing factors for CAD.