Nondestructive and three-dimensional visualization by identifying elements using synchrotron radiation microscale X-ray CT reveals microbial and cavity distributions in anaerobic granular sludge.

We developed a nondestructive three-dimensional microbial visualization method utilizing synchrotron radiation X-ray microscale computed tomography to better understand the relationship between microorganisms and their surrounding habitats. The method was tested and optimized using a mixture of axenic Escherichia coli and Comamonas testosteroni. The osmium-thiocarbohydrazide-osmium method was used to stain all the microbial cells, and gold in situ hybridization was used to detect specific phylogenetic microbial groups. The stained samples were embedded in epoxy resin for microtomographic analysis. Differences in X-ray absorbances were calculated by subtracting the pre-L3-edge images from the post-L3-edge images to visualize the osmium and gold signals. Although we successfully detected cells stained with osmium, those labeled with gold were not detected, probably because of the insufficient density of gold atoms in the microbial cells. We then applied the developed technique to anaerobic granules and visualized the distribution of microbial cells and extracellular polymeric substances. Empty spaces were highlighted to determine the cavity distribution in granules. Numerous independent cavities of different sizes were identified in the granules. The developed method can be applied to various environmental samples for deeper insights into microbial life in their habitats. IMPORTANCE: Microorganisms inhabit diverse environments and often form biofilms. One factor that affects their community structure is the surrounding physical environment. The arrangement of residential space within the formed biofilm plays a crucial role in the supply and transportation of substances, as well as the discharge of metabolites. Conventional approaches, such as scanning electron microscopy and confocal laser scanning microscopy combined with fluorescence in situ hybridization, have limitations as they provide information primarily from the biofilm surface and cross-sections. In this study, we developed a method for detecting microorganisms in biofilms using synchrotron radiation X-ray microscale computer tomography. The developed method allows nondestructive three-dimensional observation of biofilms at a single-cell resolution (voxel size of approximately 200 nm), facilitating an understanding of the relationship between microorganisms and their physical habitats.

Hepatic function markers as prognostic factors in patients with acute kidney injury undergoing continuous renal replacement therapy.

Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), secondary to cardiovascular disease and sepsis, is associated with high in-hospital mortality. Although studies have examined cardiovascular disease and sepsis in AKI, the association between AKI and hepatic functional impairment remains unclear. We hypothesized that hepatic function markers would predict mortality in patients undergoing CRRT. We included 1,899 CRRT patients from a multi-centre database. In Phase 1, participants were classified according to the total bilirubin (T-Bil) levels on the day of, and 3 days after, CRRT initiation: T-Bil < 1.2, 1.2 ≤ T-Bil < 2, and T-Bil ≥ 2 mg/dL. In Phase 2, propensity score matching (PSM) was performed to examine the effect of a T-Bil cutoff of 1.2 mg/dL (supported by the Sequential Organ Failure Assessment score); creating two groups based on a T-Bil cutoff of 1.2 mg/dL 3 days after CRRT initiation. The primary endpoint was total mortality 90 days after CRRT initiation, which was 34.7% (n = 571). In Phase 1, the T-Bil, aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT (De Ritis ratio) levels at CRRT initiation were not associated with the prognosis, while T-Bil, AST, and the De Ritis ratio 3 days after CRRT initiation were independent factors. In Phase 2, T-Bil ≥1.2 mg/dL on day 3 was a significant independent prognostic factor, even after PSM [hazard ratio: 2.41 (95% CI; 1.84-3.17), p < 0.001]. T-Bil ≥1.2 mg/dL 3 days after CRRT initiation predicted 90-day mortality. Changes in hepatic function markers in acute renal failure may enable stratification of high-risk patients.

Impact of Red Blood Cell Transfusion on Subsequent Cardiovascular Events in Patients with Acute Heart Failure and Anemia.

Red blood cell (RBC) transfusion therapy is often performed in patients with acute heart failure (AHF) and anemia; however, its impact on subsequent cardiovascular events is unclear. We examined whether RBC transfusion influences major adverse cardiovascular events (MACE) after discharge in patients with AHF and anemia.We classified patients with AHF and anemia (nadir hemoglobin level < 10 g/dL) according to whether they received RBC transfusion during hospitalization. The endpoint was MACE (composite of all-cause death, non-fatal acute coronary syndrome/stroke, or heart failure readmission) 180 days after discharge. For survival analysis, we used propensity score matching analysis with the log-rank test. As sensitivity analysis, we performed inverse probability weighting analysis and multivariable Cox regression analysis.Among 448 patients with AHF and anemia (median age, 81 years; male, 55%), 155 received RBC transfusion and 293 did not. The transfused patients had worse clinical features than the non-transfused patients, with lower levels of nadir hemoglobin and serum albumin and a lower estimated glomerular filtration rate. In the propensity-matched cohort of 87 pairs, there was no significant difference in the MACE-free survival rate between the 2 groups (transfused, 73.8% vs. non-transfused, 65.3%; P = 0.317). This result was consistent in the inverse probability weighting analysis (transfused, 76.0% vs. non-transfused, 68.7%; P = 0.512), and RBC transfusion was not significantly associated with post-discharge MACE in the multivariable Cox regression analysis (adjusted hazard ratio: 1.468, 95% confidence interval: 0.976-2.207; P = 0.065).In conclusion, this study suggests that RBC transfusions for anemia may not improve clinical outcomes in patients with AHF.

Prehospital ABC (Age, Bystander and Cardiogram) scoring system to predict neurological outcomes of cardiopulmonary arrest on arrival: post hoc analysis of a multicentre prospective observational study.

BACKGROUND: There is currently limited evidence to guide prehospital identification of patients with cardiopulmonary arrest on arrival (CPAOA) to hospital who have potentially favourable neurological function. This study aimed to develop a simple scoring system that can be determined at the contact point with emergency medical services to predict neurological outcomes. METHODS: We analysed data from patients with CPAOA using a regional Japanese database (SOS-KANTO), from January 2012 to March 2013. Patients were randomly assigned into derivation and validation cohorts. Favourable neurological outcomes were defined as cerebral performance category 1 or 2. We developed a new scoring system using logistic regression analysis with the following predictors: age, no-flow time, initial cardiac rhythm and arrest place. The model was internally validated by assessing discrimination and calibration. RESULTS: Among 4907 patients in the derivation cohort and 4908 patients in the validation cohort, the probabilities of favourable outcome were 0.9% and 0.8%, respectively. In the derivation cohort, age ≤70 years (OR 5.11; 95% CI 2.35 to 11.14), no-flow time ≤5 min (OR 4.06; 95% CI 2.06 to 8.01) and ventricular tachycardia or fibrillation as initial cardiac rhythm (OR 6.66; 95% CI 3.45 to 12.88) were identified as predictors of favourable outcome. The ABC score consisting of Age, information from Bystander and Cardiogram was created. The areas under the receiver operating characteristic curves of this score were 0.863 in the derivation and 0.885 in the validation cohorts. Positive likelihood ratios were 6.15 and 6.39 in patients with scores >2 points and were 11.06 and 17.75 in those with 3 points. CONCLUSION: The ABC score showed good accuracy for predicting favourable neurological outcomes in patients with CPAOA. This simple scoring system could potentially be used to select patients for extracorporeal cardiopulmonary resuscitation and minimise low-flow time.

In Situ Observation of the Movement of Magnetic Particles in Polyurethane Elastomer Densely Packed Magnetic Particles Using Synchrotron Radiation X-ray Computed Tomography.

In situ observation of the migration and structure formation of magnetic particles in polyurethane elastomers was carried out by X-ray computed tomography using synchrotron radiation. The mean diameter of the magnetic particles was 7.0 µm, and the volume fraction was ϕ= 0.24 at its maximum. The exposure time was 100 ms/frame, and the pixel size was 0.458 µm/pixel. The orientation angle and the volume fraction of the maximum aggregate were analyzed using commercial software for image analysis. The orientation angle for magnetic elastomers with ϕ = 0.24 was approximately 55° at 0 mT and decreased remarkably with the magnetic field. At magnetic fields above 150 mT, the orientation angle gradually decreased with the field and showed a constant value of 38° at 300 mT, suggesting that magnetic particles move and form a chain-like structure although the chains do not align perfectly in the direction of the magnetic field. On the other hand, the volume fraction of the maximum aggregate was constant at magnetic fields below 100 mT, and it significantly increased with the field, indicating that magnetic particles were connected to each other and developed into a macroscopic structure with anisotropy. Dynamic viscoelastic measurements revealed that the storage modulus of the magnetic elastomers cannot be simply scaled by the orientation angle. It was also found that the volume fraction of the maximum aggregate is a good parameter for explaining the huge increase in the storage modulus. The dynamic movement of magnetic particles when a magnetic field of 300 mT was switched on and off was also successfully observed. When the field was switched on, magnetic particles connected instantly and their aggregates were rapidly elongated in the direction of the magnetic field. When the field was switched off, some of the connections between aggregates were broken; however, most of the aggregates did not return to the original position even 5 min after being switched off.

Effects of 1,5-anhydro-D-glucitol on insulin secretion both in in vitro and ex vivo pancreatic preparations.

Organ bath experiments are conventionally used to investigate the physiological actions and effects of hormones and drugs on organ responses. We developed an experimental method to reproduce insulin secretion from isolated rat pancreas preparations, to investigate substances that promote insulin secretion ex vivo. 1,5-anhydro-D-glucitol (1,5-AG) is found in foods, and exists in humans and rodents; however, whether 1,5-AG stimulates insulin secretion remains unclear. This study aimed to assess the effects of short-term 1,5-AG stimulation on insulin secretion in both ex vivo and in INS-1E (rat-derived) cells in vitro. Our results indicated that 1,5-AG had no potency to increase the proportion of insulin outflow both in ex vivo and in vitro experiments. Insulin outflow significantly increased upon stimulation with 10 µM glimepiride, a member of the sulfonylurea class of drugs, ex vivo. Glucose-stimulated insulin secretion was observed not only in INS-1E cells but also in rat pancreatic preparations. Our findings demonstrated that short-term exposure to 1,5-AG had no effect on insulin secretion in rats.

Uric acid lowering in relation to HbA1c reductions with the SGLT2 inhibitor tofogliflozin.

An integrated analysis was performed with data from 4 phase 2 and phase 3 studies of tofogliflozin in which patients with type 2 diabetes mellitus received the sodium-glucose cotransporter 2 inhibitor tofogliflozin for up to 24 weeks. Sex differences, baseline haemoglobin A1c (HbA1c) and serum uric acid (UA) levels, and log10 -transformed urinary N-acetyl-ß-D-glucosaminidase ratio were significantly correlated with the reduction in serum UA levels at both 4 and 24 weeks in multivariate analysis (respectively, P < .0001). The decrease in HbA1c levels was greatest in the group with the highest baseline HbA1c level (quartile 4; HbA1c > 8.6%) and lowest in the group with the lowest baseline HbA1c level (quartile 1; HbA1c ≤ 7.4%). The decrease in serum UA levels was greatest in the quartile 1 group and lowest in the quartile 4 group. In most groups, the maximum decrease in serum UA levels was seen in the first 4 weeks, while the maximum decrease in HbA1c was seen at week 24. Thus, serum UA levels were significantly decreased in patients with moderate HbA1c levels.

Novel α-Galactosidase A Mutation (K391E) in a Young Woman With Severe Cardiac and Renal Manifestations of Fabry Disease.

Fabry disease, an X-linked lysosomal storage disorder due to α-galactosidase A deficiency, is associated with dysfunction of various cell types and results in a systemic vasculopathy. We describe a 29-year-old woman with Fabry disease presenting with severe cardiac and renal manifestations. Gene analysis demonstrated a novel mutation (K391E) in the GLA gene. Enzyme replacement therapy (ERT) was started with agalsidase-ß after confirming the diagnosis of Fabry disease, resulting in normalization of LV systolic function and improvement of renal function. As early therapy is crucial for preventing life-threatening sequelae, clinicians should consider Fabry disease in young patients presenting with cardiac and renal disease without any likely causes.

The ABC (Age, Bystander, and Cardiogram) score for predicting neurological outcomes of cardiac arrests without pre-hospital return of spontaneous circulation: A nationwide population-based study.

Aim: We previously proposed the ABC score to predict the neurological outcomes of cardiac arrest without prehospital return of spontaneous circulation (ROSC). Using nationwide population-based data, this study aimed to validate the ABC score through various resuscitation guideline periods. Methods: We analysed cases with cardiac arrest due to internal causes and failure to achieve prehospital ROSC in the All-Japan Utstein Registry. Patients from the 2007-2009, 2012-2014, and 2017-2019 periods were classified into the 2005, 2010, and 2015 guideline groups, respectively. Neurological outcomes were assessed using cerebral performance categories (CPCs) one month after the cardiac arrest. We defined CPC 1-2 as a favourable outcome. We evaluated the test characteristics of the ABC score, which could range from 0 to 3. Results: Among the 162,710, 186,228, and 190,794 patients in the 2005, 2010, and 2015 guideline groups, 0.7%, 0.8%, and 0.9% of the patients had CPC 1-2, respectively. The proportions of CPC 1-2 were 2.9%, 3.6%, and 4.6% in patients with ABC scores of 2 and were 9.5%, 13.3%, and 16.8% in patients with ABC scores of 3, respectively. Among patients with ABC scores of 0, 0.2%, 0.1%, and 0.2%, all had CPC 1-2, respectively. The areas under the receiver operating characteristic curves for the ABC score were 0.798, 0.822, and 0.828, respectively. Conclusions: The ABC score had acceptable discrimination for neurological outcomes in patients without prehospital ROSC in the three guideline periods.

Ascites Caused by Intestinal Anisakiasis: A Case Report and Literature Review.

Anisakiasis is a parasitic infection affecting the human gastrointestinal tract. It is caused by the consumption of contaminated, raw or inadequately cooked fish or squid, which is typically used for making sushi and sashimi. Most cases involve gastric anisakiasis, whereas intestinal anisakiasis is rare. This report describes the case of a 63-year-old Japanese woman with a history of raw fish consumption who presented with acute-onset abdominal pain and vomiting. Abdominal computed tomography (CT) demonstrated thickened small bowel loops and ascites on the liver surface. The patient was admitted for supportive care. On the second day of hospitalization, contrast-enhanced abdominal CT revealed that the ascites had moved from the liver surface to the pouch of Douglas. On the fifth day of hospitalization, the patient was discharged with a substantial improvement in abdominal pain. Five days after the discharge, her eosinophil count was elevated, and parasitic disease was therefore suspected. Anti-Anisakis IgG/A and IgE (RAST) antibody levels were elevated, confirming the diagnosis of intestinal anisakiasis. A review of 51 reported cases of intestinal anisakiasis suggests that the presence of ascites and measurement of anti-Anisakis antibody titers are helpful for diagnosis in cases presenting with nonspecific abdominal symptoms after consumption of raw or undercooked fish.

Near-infrared focused heating method for the rotational diamond anvil cell.

We developed a near-infrared focused heating system (IRrDAC) for deformation experiments using a rotational diamond anvil cell. This study reports the results of annealing tests on silver and antigorite conducted at SPring-8 (BL47XU) using the IRrDAC system. The experimental results demonstrated the melting of silver and the dehydration of antigorite, confirming the capability of this system. The reproducible relationships between temperature and input power were also confirmed. The IRrDAC system enables deformation experiments at pressures equivalent to those of the lower mantle under homogeneous and stable temperatures and is expected to contribute to the understanding of deep Earth rheology.

Microstructural and chemical features of impact melts on Ryugu particle surfaces: Records of interplanetary dust hit on asteroid Ryugu.

The Hayabusa2 spacecraft delivered samples of the carbonaceous asteroid Ryugu to Earth. Some of the sample particles show evidence of micrometeoroid impacts, which occurred on the asteroid surface. Among those, particles A0067 and A0094 have flat surfaces on which a large number of microcraters and impact melt splashes are observed. Two impact melt splashes and one microcrater were analyzed to unveil the nature of the objects that impacted the asteroid surface. The melt splashes consist mainly of Mg-Fe-rich glassy silicates and Fe-Ni sulfides. The microcrater trapped an impact melt consisting mainly of Mg-Fe-rich glassy silicate, Fe-Ni sulfides, and minor silica-rich glass. These impact melts show a single compositional trend indicating mixing of Ryugu surface materials and impactors having chondritic chemical compositions. The relict impactor in one of the melt splashes shows mineralogical similarity with anhydrous chondritic interplanetary dust particles having a probable cometary origin. The chondritic micrometeoroids probably impacted the Ryugu surface during its residence in a near-Earth orbit.

Comparison of perfusion-metabolism mismatch in 99mTc-MIBI and 123I-BMIPP scintigraphy with cardiac magnetic resonance in patients with dilated cardiomyopathy.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging is an established method of detecting myocardial fibrosis related to prognosis in patients with dilated cardiomyopathy (DCM). Recent studies have found that (99m)Tc-methoxy-isobutyl-isonitrile (MIBI) and (123)I-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) dual single-photon-emission computerized tomography (MIBI-BMIPP dual SPECT) can detect perfusion-metabolism mismatches. We compared MIBI-BMIPP dual SPECT with CMR findings and assessed their prognostic abilities to determine the significance of abnormal metabolism in patients with DCM. METHODS AND RESULTS: Fifty inpatients with DCM (age 58 ± 12 y; 14 female) were assessed with the use of MIBI-BMIPP dual SPECT and CMR. Perfusion-metabolism mismatches were identified mainly at the left ventricular free wall, whereas late gadolinium enhancement (LGE) was evident mostly at the septal wall. During a median follow-up of 33 months, 9 patients developed cardiac events including death, heart failure, and fatal arrhythmia. Event-free survival rates were significantly lower for patients with LGE plus a mismatch than with other abnormalities (P = .001). Among clinical and imaging variables, LGE plus a mismatch was significantly associated with cardiac events (hazard ratio 7.9, 95% confidence interval 1.8-35.6; P = .007). CONCLUSIONS: Coexisting LGE and a perfusion-metabolism mismatch accurately predict future cardiac events in patients with DCM.

A Case of Fever, Impaired Consciousness, and Psychosis Caused by Nitrous Oxide Abuse and Misdiagnosed as Acute Meningitis.

Nitrous oxide (N2O) is readily available, and its abuse for recreational purposes has become a social problem. In Japan, where N2O is strictly prohibited for non-medical use, abuse is often overlooked due to a lack of experience in the field. N2O abuse causes various long-term symptoms, including vitamin B12 deficiency, myelopathy, myeloneuropathy, subacute combined degeneration, mood changes, and psychosis. The diagnosis of N2O abuse is difficult due to the compound's short half-life and rapid elimination through the lungs. This report describes a case of fever and impaired consciousness in a patient with a history of N2O abuse.

Utility of fractional excretion of urea nitrogen in heart failure patients with chronic kidney disease.

AIMS: Maintenance of euvolaemia with diuretics is critical in heart failure (HF) patients with chronic kidney disease (CKD); however, it is challenging because no reliable marker of volume status exists. Fractional excretion of urea nitrogen (FEUN) is a useful index of volume status in patients with renal failure. We aimed to examine whether FEUN is a surrogate marker of volume status for risk stratification in HF patients with CKD. METHODS AND RESULTS: We examined 516 HF patients with CKD (defined as discharge estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) whose FEUN was measured at discharge (median age, 80 years; 58% male). The patients were divided into four groups according to quartile FEUN value at discharge: low-FEUN, FEUN ≤ 32.1; medium-FEUN, 32.1 < FEUN ≤ 38.0; high-FEUN, 38.0 < FEUN ≤ 43.7; and extremely-high-FEUN, FEUN > 43.7. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). During the 3 year follow-up, 131 HF readmissions occurred. Kaplan-Meier analysis showed that the HF readmission rate was significantly lower in the medium-FEUN group than in the other three groups (log-rank test, P = 0.029). Multivariate Cox regression analysis identified the low-FEUN, high-FEUN, and extremely-high-FEUN values as independent factors associated with post-discharge HF readmission. In the analysis of 130 patients who underwent right heart catheterization during hospitalization, a significant correlation between FEUN value and right atrial pressure was observed (R = 0.243, P = 0.005). Multivariate linear regression analysis revealed that FEUN value at discharge decreased in a dose-dependent manner with loop diuretics. CONCLUSIONS: In HF patients with CKD, FEUN is a potential marker of volume status for risk stratification of post-discharge HF readmission. Low FEUN value (FEUN ≤ 32.1) may represent intravascular dehydration, whereas high FEUN value (FEUN > 38.0) may represent residual congestion; both of them were independent risk factors for HF readmission. FEUN may be useful to determine euvolaemia and guide fluid management in HF patients with CKD.

A dehydrated space-weathered skin cloaking the hydrated interior of Ryugu.

Without a protective atmosphere, space-exposed surfaces of airless Solar System bodies gradually experience an alteration in composition, structure and optical properties through a collective process called space weathering. The return of samples from near-Earth asteroid (162173) Ryugu by Hayabusa2 provides the first opportunity for laboratory study of space-weathering signatures on the most abundant type of inner solar system body: a C-type asteroid, composed of materials largely unchanged since the formation of the Solar System. Weathered Ryugu grains show areas of surface amorphization and partial melting of phyllosilicates, in which reduction from Fe3+ to Fe2+ and dehydration developed. Space weathering probably contributed to dehydration by dehydroxylation of Ryugu surface phyllosilicates that had already lost interlayer water molecules and to weakening of the 2.7 µm hydroxyl (-OH) band in reflectance spectra. For C-type asteroids in general, this indicates that a weak 2.7 µm band can signify space-weathering-induced surface dehydration, rather than bulk volatile loss.

Disruption of atherosclerotic neointima seven years after bare metal stent deployment.

A 58-year-old male with a history of prior myocardial infarction, hypertension, and dyslipidemia was admitted due to deteriorating exertional angina. A bare metal stent (Multilink plus™, GUIDANT Corporation, Santa Clara, CA, USA) had been implanted into the proximal left anterior descending artery because of ST-elevation myocardial infarction 7 years earlier. Optical coherence tomography (OCT) showed a disruption of the atherosclerotic neointima overlying the stent. Intravascular imaging studies and pathological studies have shown that neointima within a bare-metal stent often transform into atherosclerotic tissue during an extended period of time. In the current report, OCT demonstrated that a disruption of the atherosclerotic neointima has the potential to cause the development of unstable clinical features. OCT examinations therefore help to understand the pathogenesis of acute coronary syndrome after stent implantation.

Long-Term Electrocardiographic Follow-Up of a Patient with Light-Chain Cardiac Amyloidosis.

Amyloid light-chain (AL) cardiac amyloidosis can cause restrictive cardiomyopathy, which has a poor prognosis. Although electrocardiography (ECG) is useful for its diagnosis and management, there are few reports on the long-term follow-up of electrocardiographic changes in affected patients. The present patient was a 62-year-old woman who visited our hospital for assessment of palpitations and lower leg edema. A chest radiograph showed cardiac enlargement, and ECG revealed sinus rhythm, first-degree atrioventricular block, low QRS voltage in the limb leads and a pseudo-myocardial infarction pattern in the precordial leads. Echocardiography revealed left ventricular hypertrophy with systolic and diastolic dysfunction. Immunoelectrophoresis demonstrated M-protein (IgGλ), and bone marrow biopsy suggested IgGλ-type plasmacytoma. Myocardial biopsy findings were compatible with cardiac amyloidosis. On the basis of these findings, we diagnosed AL cardiac amyloidosis. Melphalan-prednisolone (MP) therapy was started in conjunction with treatment for non-sustained ventricular tachycardia and congestive heart failure. Two years and 4 months later, the sinus rhythm converted to atrial tachycardia. At a follow-up examination at 4 years and 8 months, right branch block appeared. After that, intraventricular conduction worsened, and the low voltage in the limb leads was not observed. Seven years after diagnosis, she was hospitalized for treatment of pneumonia and heart failure with tachycardia. On the seventh day of hospitalization, heart rhythm changed to atrial stand-still with escaped ventricular rhythm and she died of cardiac arrest. These ECG changes are valuable information regarding the pathophysiological changes that occur in AL cardiac amyloidosis.

SNPs on chromosome 5p15.3 associated with myocardial infarction in Japanese population.

Myocardial infarction (MI) occurs as the result of complex interactions of multiple genetic and environmental factors. By conducting a genome wide association study in a Japanese population using 210,785 single nucleotide polymorphism (SNP) markers, we identified a novel susceptible locus for MI on chromosome 5p15.3. An SNP (rs11748327) in this locus showed significant association in several independent cohorts (combined P = 5.3 × 10(-13), odds ratio = 0.80, comparison of allele frequency). Association study using tag SNPs in the same linkage disequilibrium block revealed that two additional SNPs (rs490556 and rs521660) conferred risk of MI. These findings indicate that the SNPs on chromosome 5p15.3 are novel protective genetic factors against MI.