Successful Industry-University Collaborations in Manufacturing Technology

Historically, many Japanese manufacturing companies have independently developed manufacturing technologies such as advanced processes and equipment, methods of analyzing manufacturing phenomena, and production management and quality control systems, which maintain the competitiveness of product development and production. Most of these companies are beginning to recognize the importance of collaborating with universities, where advanced technologies and methodologies are researched, as a way to adapt to the short lead-time requirements for research and development in manufacturing technology. Because of the many challenges to the success of joint research, the anticipated results are not always obtained. In this paper, key factors for the success of industry-university collaboration in the manufacturing technology field are discussed by demonstrating actual successful cases carried out by Toshiba and the University of Maryland

Association of Methylenetetrahydrofolate Reductase (MTHFR-677 and MTHFR-1298) Genetic Polymorphisms with Occlusive Artery Disease and Deep Venous Thrombosis in Macedonians

Cilj Ispitati moguću povezanost genetičkog polimorfizma metilen-tetrahidrofolatne reduktaze (MTHFR-677, MTHFR-1298) s okluzivnom arterijskom bolešću i dubokom venskom trombozom u Makedonaca. Postupci Radili smo s 83 zdrave osobe, 76 bolesnika s okluzivnom arterijskom bolešću i 67 bolesnika s dubokom venskom trombozom. Od njih su prikupljeni su uzorci krvi i iz leukocita je izolirana DNA. Mutacije gena za MTHFR identificirane su testom CVD StripAssay (ViennaLab, Labordiagnostika GmbH, Beč, Austrija), a za analizu je uporabljen sustav za genetičku analizu PyPop. Potom su izračunani Pearsonove P vrijednosti, grubi omjer izgleda (odds ratio, OR) i Waldovi 95% intervali pouzdanosti (confidence intervals, CI). Rezultati Frekvencija alela C lokusa za MTHFR-677 bila je 0,575 u bolesnika s dubokom venskom trombozom, 0,612 u onih a okluzivnom arterijskom bolešću i 0,645 u zdravih osoba. Frekvencija alela T lokusa za MTHFR-677 bila je niža u zdravih osoba (0,355) nego u bolesnika s okluzivnom arterijskom bolešću (0,388) i dubokom venskom trombozom (0,425). Frekvencija alela A u lokusu MTHFR-1298 bila je 0,729 u zdravih osoba, 0,770 u bolesnika s okluzivnom arterijskom bolešću i 0,746 u bolesnika s dubokom venskom trombozom. Frekvencija alela C lokusa za MTHFR-1298 bila je 0,271 u zdravih osoba, 0,230 u bolesnika s okluzivnom arterijskom bolešću i 0,425 u bolesnika s dubokom venskom trombozom. Nije opažena povezanost polimorfizma MTHFR-677 i MTHFR-1289 s okluzivnom arterijskom bolešću ili dubokom venskom trombozom, nego se samo pokazao protektivni učinak diplotipa MTHFR/CA:CC za okluzivnu arterijsku bolest. Zaključak Osim protektivnoga učinka diplotipa MTHFR/CA:CC za okluzivnu arterijsku bolest, nismo našli značajnu povezanost polimorfizma lokusa MTHFR-677 i MTHFR-1289 s okluzivnom arterijskom bolešću i dubokom venskom trombozom.Aim To analyze the association of methylenetetrahydrofolate reductase polymorphisms (MTHFR-677 and MTHFR-1298) with occlusive artery disease and deep venous thrombosis in Macedonians. Methods We examined 83 healthy respondents, 76 patients with occlusive artery disease, and 67 patients with deep venous thrombosis. Blood samples were collected and DNA was isolated from peripheral blood leukocytes. Identification of MTHFR mutations was done with CVD StripAssay (ViennaLab, Labordiagnostika GmbH, Vienna, Austria) and the population genetics analysis package, PyPop, was used for the analysis. Pearson P values, crude odds ratio, and Wald’s 95% confidence intervals were calculated. Results The frequency of C alleles of MTHFR-677 was 0.575 in patients with deep venous thrombosis, 0.612 in patients with occlusive artery disease, and 0.645 in healthy participants. The frequency of T allele of MTHFR-677 was lower in healthy participants (0.355) than in patients with occlusive artery disease (0.388) and deep venous thrombosis (0.425). The frequency of A allele for MTHFR-1298 was 0.729 in healthy participants, 0.770 in patients with occlusive artery disease, and 0.746 in patients with deep venous thrombosis. The frequency of C allele of MTHFR-1298 was 0.271 in healthy participants, 0.230 in patients with occlusive artery disease, and 0.425 in patients with deep venous thrombosis. No association of MTHFR-677 and MTHFR- 1289 polymorphisms with occlusive artery disease and deep venous thrombosis was found, except for the protective effect of MTHFR/CA: CC diplotype for occlusive artery disease. Conclusion We could not confirm a significant association of MTHFR- 677 and MTHFR-1289 polymorphisms with occlusive artery disease or deep venous thrombosis in Macedonians, except for the protective effect of MTHFR/CA:CC diplotype against occlusive artery disease

Artykuł oryginalny Występowanie polimorfizmu genu SERPINE1 u osób z miażdżycą zarostową tętnic kończyn dolnych lub zakrzepicą żył głębokich w populacji macedońskiej

Background: Raised SERPINE1 plasma levels are related to a 1-bp guanine deletion/insertion (4G5G) polymorphism in the promoter of the SERPINE1 (plasminogen activator inhibitor 1 – PAI1) gene. Evidence suggested that the plasma levels of SERPINE1 modulate the risk of coronary artery disease; furthermore, that the 4G5G polymorphism affects the expression of the SERPINE1 gene. Aim: To analyse association of SERPINE1 polymorphism with occlusive artery disease (OAD) and deep venous thrombosis (DVT) in Macedonians in order to investigate its role as a part of candidate genes in different vascular diseases in Macedonians. Methods: Investigated groups consisted of 82 healthy patients, 75 with OAD, and 66 with DVT. Blood samples were collected after written informed consent was obtained, and DNA was isolated from peripheral blood leukocytes. Identification of SERPINE1 polymorphism was done with CVD StripAssay (ViennaLab, Labordiagnostica GmbH, Austria). The population genetics analysis package, PyPop, was used for analysis of the SERPINE1 data. Pearson’s P-values, crude odds ratio and Wald’s 95% CI were calculated with Bonferroni corrected p value. Results: The frequency of 4G allele for SERPINE1 was 0.538 for DVT, 0.555 for healthy participants, and 0.607 for OAD. The frequency of 5G allele for SERPINE1 was the smallest in patients with OAD (0.393) and was higher in healthy participants (0.445), and patients with DVT (0.462). Test of neutrality (Fnd) showed negative value, but was significantly different from 0 for SERPINE1 in healthy participants (p of F = 0.041) and in patients with DVT (p of F = 0.030). SERPINE1 genotypes in healthy participants and patients with OAD were not in Hardy Weinberg proportions (p = 0.019 and 0.001, respectively). No association between SERPINE1 polymorphisms and OAD or DVT was found. Conclusion: There is no significant relationship between SERPINE1 polymorphisms and occlusive artery disease or deep venous thrombosis in Macedonian population.Wstęp: Zwiększone stężenie SERPINE1 jest związane z polimorfizmem delecji/wstawienia 1-bp guaniny (4G5G) do promotora genu SERPINE1 (ang. plasminogen activator inhibitor 1, PAI1). Wykazano, że stężenie osoczowe SERPINE1 ma wpływ na ryzyko wystąpienia choroby wieńcowej. Ponadto wiadomo, że polimorfizm 4G5G wpływa na ekspresję genu SERPINE1. Cel: Ocena związku pomiędzy występowaniem polimorfizmu genu SERPINE1 a miażdżycą zarostową tętnic kończyn dolnych (OAD) lub zakrzepicą żył głębokich (DVT) u mieszkańców Macedonii. Metody: Badaniami objęto grupę 82 zdrowych osób, 75 chorych z OAD oraz 66 chorych z DVT. Po uzyskaniu zgody pobierano krew i izolowano DNA z leukocytów krwi obwodowej. Polimorfizm genu SERPINE1 badano za pomocą CVD StripAssay (ViennaLab, Labordiagnostica GmbH, Austria). Do analizy statystycznej polimorfizmu SERPINE1 użyto populacyjnego programu PyPop. Wyniki: Częstość występowania allela 4G dla SERPINE1 wynosiła 0,538 w grupie DVT, 0,555 w grupie osób zdrowych oraz 0,607 w grupie OAD. Częstość występowania allela 5G dla SERPINE1 była najniższa w grupie OAD (0,393), pośrednia u osób zdrowych (0,445), a najwyższa w grupie DVT (0,462). Test neutralności (Fnd) miał wartości ujemne, ale był istotnie różny od 0 dla genu SERPINE1 u osób zdrowych (p dla testu F = 0,041) i chorych z DVT (p dla testu F = 0,030). U osób zdrowych i chorych z OAD genotypy SERPINE1 nie układały się w proporcji Hardy’ego-Weinberga (odpowiednio, p = 0,019 i 0,001). Wnioski: Nie znaleziono związku pomiędzy polimorfizmem genu SERPINE1 a OAD lub DVT u mieszkańców Macedonii

Artykuł oryginalnyZwiązek pomiędzy występowaniem polimorfizmu genu 22 cytokiny a kardiomiopatią rozstrzeniową w populacji chorych z Macedonii

Background: Inflammation is an important component in the pathogenesis of many cardiovascular diseases and one of the commonest mechanisms in cardiomyopathy. There have been several studies on the cytokine polymorphism and dilated cardiomyopathy (DCM), but the results obtained were contradictory. Aim: To examine a possible role of 22 cytokine gene polymorphisms in host susceptibility to or protection against DCM in Macedonians. Methods: In this study 301 healthy unrelated individuals and 52 patients with DCM were studied. Cytokine genotyping was performed by PCR with sequence-specific priming (PCR-SSP) (Heidelberg kit). Results: After the Bonferroni adjustment, the IL-4 -1098/T, IL-4 -1098/T:T, IL-4/TCC, and IL-4/TCC:TTC cytokine genes were positively associated with DCM, while a negative association was identified for IL-4 -1098/G, IL-4 -1098/G:T, IL-1B +3962/C:C, IL-4/GCC, and IL-4/GCC:TTC. Conclusions: These results suggest that some cytokine gene polymorphisms are significantly associated and affect host susceptibility/resistance to DCM in Macedonians.Wstęp: Zapalenie jest jednym z istotnych czynników patogenetycznych wielu chorób układu sercowo-naczyniowego i częstym mechanizmem powstawania kardiomiopatii. W wielu badaniach analizowano związki pomiędzy polimorfizmem genu cytokiny a kardiomiopatią rozstrzeniową (DCM), ale wyniki były rozbieżne. Cel: Zbadanie związku pomiędzy występowaniem polimorfizmu genu 22 cytokiny a DCM w populacji macedońskiej. Metody: Grupa badana składała się z 301 zdrowych ochotników i 52 chorych z DCM. Badania genetyczne wykonano techniką łańcuchowej reakcji polimerazy (ang. polymerase chain reaction, PCR). Wyniki: Po zastosowaniu poprawki Bonferroniego okazało się, że występowanie IL-4 -1098/T, IL-4 -1098/T:T, IL-4/TCC, i IL-4/TCC:TTC było pozytywnie związane z obecnością DCM, podczas gdy występowanie IL-4 -1098/G, IL-4 -1098/G:T, IL-1b +3962/C:C, IL-4/GCC, i IL-4/GCC:TTC było negatywnie związane z obecnością tej choroby. Wnioski: Powyższe wyniki wskazują, że niektóre polimorfizmy genu cytokiny 22 są związane z występowaniem DCM w populacji macedońskiej

Time From First Medical Contact to Aspirin in ST Elevation Myocardial Infarction: An International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) Study

BACKGROUND: A significant number of patients who suffer from STEMI do not reach a hospital within the recommended timeframe in the South Eastern European countries. Unequal dispersion of PCI-capable facilities throughout this area results in transport distances that can exceed 100 miles, while response times vary greatly dependent upon volunteer ambulance services. METHODS: The aim of the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC /NCT01218776 ) registry was to assess whether initial antiplatelet/ anticoagulant treatment at the point of prehospital first medical contact impacts in-hospital outcomes. To assess the value of this strategy were compared: prehospital versus in-hospital first medical contact; those arriving at the hospital by ambulance versus those whose initial hospital care was an ambulatory/community center. RESULTS: Of the 2295 patients enrolled in the study, 392 received fibrinolysis, 753 primary PCI, 86 facilitated PCI, and 1064 standard medical therapy having overcome the golden hours for reperfusion therapy. Compared with the in-hospital group, patients who underwent facilitated PCI (7%, n=34) experienced 9.6 % reduction in cardiovascular mortality (odd ratio [OR] 0.096 coefficient interval [C.I] 0.012-0.69 P=0.004). Arrival by an ambulatory/community center incurred a substantial delay from first medical contact to reperfusion (fibrinolysis 76 min [63 min to 105 min] and PCI 35 min [224 min to 612 min]) compared with arrival by ambulance (fibrinolysis 47 min [32 min to 68 min] and PCI 108 min [85 min to 150 min]). CONCLUSIONS: These findings support prehospital antiplatelet/ anticoagulant treatment followed by reperfusion therapy in patients presenting early with STEMI, who do not have access to hospital care within the recommended time-frame of 60 minutes from first medical contact. Those activating the prehospital medical response system without receiving prehospital ambulance assignment experienced the longest delay from first medical contact to reperfusion, indicating a lost opportunity to enhance ST elevation myocardial infarction patient outcomes

Association of Methylenetetrahydrofolate Reductase (MTHFR-677 and MTHFR-1298) Genetic Polymorphisms with Occlusive Artery Disease and Deep Venous Thrombosis in Macedonians

Cilj Ispitati moguću povezanost genetičkog polimorfizma metilen-tetrahidrofolatne reduktaze (MTHFR-677, MTHFR-1298) s okluzivnom arterijskom bolešću i dubokom venskom trombozom u Makedonaca. Postupci Radili smo s 83 zdrave osobe, 76 bolesnika s okluzivnom arterijskom bolešću i 67 bolesnika s dubokom venskom trombozom. Od njih su prikupljeni su uzorci krvi i iz leukocita je izolirana DNA. Mutacije gena za MTHFR identificirane su testom CVD StripAssay (ViennaLab, Labordiagnostika GmbH, Beč, Austrija), a za analizu je uporabljen sustav za genetičku analizu PyPop. Potom su izračunani Pearsonove P vrijednosti, grubi omjer izgleda (odds ratio, OR) i Waldovi 95% intervali pouzdanosti (confidence intervals, CI). Rezultati Frekvencija alela C lokusa za MTHFR-677 bila je 0,575 u bolesnika s dubokom venskom trombozom, 0,612 u onih a okluzivnom arterijskom bolešću i 0,645 u zdravih osoba. Frekvencija alela T lokusa za MTHFR-677 bila je niža u zdravih osoba (0,355) nego u bolesnika s okluzivnom arterijskom bolešću (0,388) i dubokom venskom trombozom (0,425). Frekvencija alela A u lokusu MTHFR-1298 bila je 0,729 u zdravih osoba, 0,770 u bolesnika s okluzivnom arterijskom bolešću i 0,746 u bolesnika s dubokom venskom trombozom. Frekvencija alela C lokusa za MTHFR-1298 bila je 0,271 u zdravih osoba, 0,230 u bolesnika s okluzivnom arterijskom bolešću i 0,425 u bolesnika s dubokom venskom trombozom. Nije opažena povezanost polimorfizma MTHFR-677 i MTHFR-1289 s okluzivnom arterijskom bolešću ili dubokom venskom trombozom, nego se samo pokazao protektivni učinak diplotipa MTHFR/CA:CC za okluzivnu arterijsku bolest. Zaključak Osim protektivnoga učinka diplotipa MTHFR/CA:CC za okluzivnu arterijsku bolest, nismo našli značajnu povezanost polimorfizma lokusa MTHFR-677 i MTHFR-1289 s okluzivnom arterijskom bolešću i dubokom venskom trombozom.Aim To analyze the association of methylenetetrahydrofolate reductase polymorphisms (MTHFR-677 and MTHFR-1298) with occlusive artery disease and deep venous thrombosis in Macedonians. Methods We examined 83 healthy respondents, 76 patients with occlusive artery disease, and 67 patients with deep venous thrombosis. Blood samples were collected and DNA was isolated from peripheral blood leukocytes. Identification of MTHFR mutations was done with CVD StripAssay (ViennaLab, Labordiagnostika GmbH, Vienna, Austria) and the population genetics analysis package, PyPop, was used for the analysis. Pearson P values, crude odds ratio, and Wald’s 95% confidence intervals were calculated. Results The frequency of C alleles of MTHFR-677 was 0.575 in patients with deep venous thrombosis, 0.612 in patients with occlusive artery disease, and 0.645 in healthy participants. The frequency of T allele of MTHFR-677 was lower in healthy participants (0.355) than in patients with occlusive artery disease (0.388) and deep venous thrombosis (0.425). The frequency of A allele for MTHFR-1298 was 0.729 in healthy participants, 0.770 in patients with occlusive artery disease, and 0.746 in patients with deep venous thrombosis. The frequency of C allele of MTHFR-1298 was 0.271 in healthy participants, 0.230 in patients with occlusive artery disease, and 0.425 in patients with deep venous thrombosis. No association of MTHFR-677 and MTHFR- 1289 polymorphisms with occlusive artery disease and deep venous thrombosis was found, except for the protective effect of MTHFR/CA: CC diplotype for occlusive artery disease. Conclusion We could not confirm a significant association of MTHFR- 677 and MTHFR-1289 polymorphisms with occlusive artery disease or deep venous thrombosis in Macedonians, except for the protective effect of MTHFR/CA:CC diplotype against occlusive artery disease

Methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genotypes and haplotypes and plasma homocysteine levels in patients with occlusive artery disease and deep venous thrombosis

The aim was to investigate different genotypes and haplotypes of methylenetetrahydrofolate reductase (MTHFR-677, -1298) and plasma concentration of total homocysteine (tHcy) in Macedonian patients with occlusive artery disease (OAD) and deep venous thrombosis (DVT). Investigated groups consists of 80 healthy, 74 patients with OAD, and 63 patients with DVT. Plasma tHcy was measured with Microplate Enzyme Immunoassay. Identification of MTHFR genotypes and haplotypes was done with CVD StripAssay. The probability level (P-value) was evaluated by the Student's t-test. Plasma concentration of tHcy in CC and CT genotypes of MTHFR C677T was significantly increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy in AC genotype of MTHFR A1298C was increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy was significantly increased in AA genotype of patients with OAD, but not in patients with DVT. We found a significant increase of plasma tHcy in patients with OAD in comparison with healthy respondents for normal:heterozygote (CC:AC), heterozygote:normal (CT:AA), and heterozygote:heterozygote (CT:AC) haplotypes. Plasma concentration of tHcy in patients with DVT in comparison with healthy respondents was significantly increased for normal:normal (CC:AA), normal heterozygote (CC:AC), and heterozygote:heterozygote (CT:AC) haplotypes. We conclude that MTHFR C677T and MTHFR A1289C genotypes and haplotypes are connected with tHcy plasma levels in Macedonian patients with OAD and DVT

ROUTINE PERCUTANEOUS CORONARY INTERVENTION VERSUS MEDICAL THERAPY IN CLINICAL PRACTICE: THE ISACS-TC REGISTRY

Background: The role of revascularization with percutaneous coronary intervention (PCI) in the management of Unstable Angina and Non-ST-Elevation Myocardial Infarction (UA/NSTEMI) remains controversial. Previous post hoc analysis of randomized clinical trials has shown that troponin elevation permits the determination of high-risk patients who may benefit more from PCI. We further explored this hypothesis in clinical practice, attempting to address previous concerns on baseline risk of patients as assessed by biomarker status (UA versus NSTEMI). Methods: The study population of the present analysis consists of the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC/NCT01218776) registry participants. This is an observational study of 1940 UA/NSTEMI patients; of these 805 underwent routine PCI and 1135 received medical therapy (MT) alone. The primary outcome was all-cause in-hospital mortality. Results: Patients treated with MT alone included a greater number of females (37% versus 26.21%, p<0.001), had higher rates of cerebrovascular disease (7.22% versus 3.11%, p=0.0001), of diabetes (30.6% versus 21.53%, p<0.001) and Killip class 65 2 (21.10% versus 17.07%, p=0.1759), but lower rates of smoking (24.55% versus 40.30%, p<0.001) and hypercholesterolemia (42.76% versus 46.41%, p=0.1466) than their counterpart undergoing PCI. In multivariable regression analysis, in-hospital revascularization was independently associated with a reduction of the primary outcome when compared with MT: adjusted odd ratio (OR) 0.37 (95% confidence interval [CI]: 0.19\u20130.72, p=0.003] and 3.24 (95%CI 1.44 \u2013 7.30, p=0.004). Analysis restricted to patients with NSTEMI showed attenuation in the effect size for all-cause mortality: adjusted OR: 0.49 ; 95% CI: 0.25\u20130.96, p=0.037 and 2.32 (95% CI: 1.02 \u2013 5.29, p=0.045). Conclusions: Contrary to expectations, a routine strategy with PCI was associated with greater benefits in patients with negative troponin status ( UA). Potential clinical benefits from PCI do not seem to favorably affect the overall prognosis of the index myocardial infarction (NSTEMI). Larger randomized studies are required to prove this conclusively