Isolation, Characterization, and Safety Evaluation of the Novel Probiotic Strain Lacticaseibacillus paracasei IDCC 3401 via Genomic and Phenotypic Approaches.

This study aimed to explore the safety and properties of Lacticaseibacillus paracasei IDCC 3401 as a novel probiotic strain via genomic and phenotypic analyses. In whole-genome sequencing, the genes associated with antibiotic resistance and virulence were not detected in this strain. The minimum inhibitory concentration test revealed that L. paracasei IDCC 3401 was susceptible to all the antibiotics tested, except for kanamycin. Furthermore, the strain did not produce toxigenic compounds, such as biogenic amines and D-lactate, nor did it exhibit significant toxicity in a single-dose acute oral toxicity test in rats. Phenotypic characterization of carbohydrate utilization and enzymatic activities indicated that L. paracasei IDCC 3401 can utilize various nutrients, allowing it to grow in deficient conditions and produce health-promoting metabolites. The presence of L. paracasei IDCC 3401 supernatants significantly inhibited the growth of enteric pathogens (p < 0.05). In addition, the adhesion ability of L. paracasei IDCC 3401 to intestinal epithelial cells was found to be as superior as that of Lacticaseibacillus rhamnosus GG. These results suggest that L. paracasei IDCC 3401 is safe for consumption and provides health benefits to the host.

Effect of Bacteriocin-Like Inhibitory Substance (BLIS) from Enterococcus faecium DB1 on Cariogenic Streptococcus mutans Biofilm Formation.

The aim of the study was to investigate the effect of bacteriocin-like inhibitory substance (BLIS) from Enterococcus faecium DB1 on cariogenic Streptococcus mutans biofilm. Crystal violet staining, fluorescence, and scanning electron microscopy analyses demonstrated that the BLIS from Enterococcus faecium DB1 (DB1 BLIS) inhibited S. mutans biofilm. When DB1 BLIS was co-incubated with S. mutans, biofilm formation by S. mutans was significantly reduced (p<0.05). DB1 BLIS also destroyed the preformed biofilm of S. mutans. In addition, DB1 BLIS decreased the viability of S. mutans biofilm cells during the development of biofilm formation and in the preformed biofilm. DB1 BLIS significantly decreased the growth of S. mutans planktonic cells. Furthermore, S. mutans biofilm on the surface of saliva-coated hydroxyapatite discs was reduced by DB1 BLIS. Taken together, DB1 BLIS might be useful as a preventive and therapeutic agent against dental caries caused by S. mutans.

Caruncular lesions: A 16-year single centre review in the United Kingdom.

BACKGROUND/AIMS: To review the clinicopathological features of caruncle biopsies carried out at a district general hospital in the United Kingdom (UK), and compare with other centres where data has been published. METHODS: Retrospective, single-centre, observational case series between 2004-2020. RESULTS: A total of 31 lesions from 31 patients were analysed. 18 of 31 patients were men (58%), and the age ranged from 12 to 91 years. 13 different histopathological types of lesions were identified in our case series, including 9 melanocytic nevi (29%), 7 benign squamous papillomas (23%), 5 skin adnexal lesions (16%), 3 chronic inflammation (10%), 3 epithelial cysts (10%), 1 basal cell carcinoma (3%), 2 malignant melanomas (6%) and l lymphoproliferative disorder (3%). Pre-operative suspected diagnoses were often vague but correct in 12 of 18 cases (67%), where data was available. CONCLUSION: The uncommon nature and variety of caruncular lesions make the diagnostic process difficult. Our case series is the first reported in the UK, showing a slightly higher proportion of malignant melanomas, in keeping with the population demographics. Excisional biopsies would, therefore, be prudent in the majority of cases to rule out any possible malignancy.

Antibiofilm, AntiAdhesive and Anti-Invasive Activities of Bacterial Lysates Extracted from Pediococcus acidilactici against Listeria monocytogenes.

This study aimed to investigate whether bacterial lysates (BLs) extracted from Pediococcus acidilactici reduce Listeria monocytogenes biofilm formation, as well as adhesion to and invasion of human intestinal epithelial cells. Pretreatment with P. acidilactici BLs (20, 40, and 80 µg/mL) significantly inhibited L. monocytogenes biofilm formation on the surface of polystyrene (p < 0.05). Fluorescence and scanning-electron-microscopic analyses indicated that L. monocytogenes biofilm comprised a much less dense layer of more-dispersed cells in the presence of P. acidilactici BLs. Moreover, biofilm-associated genes, such as flaA, fliG, flgE, motB, degU, agrA, and prfA, were significantly downregulated in the presence of P. acidilactici BLs (p < 0.05), suggesting that P. acidilactici BLs prevent L. monocytogenes biofilm development by suppressing biofilm-associated genes. Although P. acidilactici BLs did not dose-dependently inhibit L. monocytogenes adhesion to and invasion of intestinal epithelial cells, the BLs effectively inhibited adhesion and invasion at 40 and 80 µg/mL (p < 0.05). Supporting these findings, P. acidilactici BLs significantly downregulated L. monocytogenes transcription of genes related to adhesion and invasion, specifically fbpA, ctaP, actA, lapB, ami, and inlA. Collectively, these results suggest that P. acidilactici BLs have the potential to reduce health risks from L. monocytogenes.

Inhibitory Effect of Bacterial Lysates Extracted from Pediococcus acidilactici on the Differentiation of 3T3-L1 Pre-Adipocytes.

Postbiotics, including bacterial lysates, are considered alternatives to probiotics. The aim of the current study was to investigate the effect of bacterial lysates (BLs) extracted from Pediococcus acidilactici K10 (K10 BL) and P. acidilactici HW01 (HW01 BL) on the differentiation of 3T3-L1 pre-adipocytes. Both K10 and HW01 BLs significantly reduced the accumulation of lipid droplets and the amounts of cellular glycerides in 3T3-L1 cells (p < 0.05). However, another postbiotic molecule, peptidoglycan of P. acidilactici K10 and P. acidilactici HW01, moderately inhibited the accumulation of lipid droplets, whereas heat-killed P. acidilactici did not effectively inhibit the lipid accumulation. The mRNA and protein levels of the transcription factors, peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α, responsible for the differentiation of 3T3-L1 cells, were significantly inhibited by K10 BL and HW01 BL (p < 0.05). Both K10 and HW01 BLs decreased adipocyte-related molecules, adipocyte fatty acid-binding protein and lipoprotein lipase, at the mRNA and protein levels. Furthermore, both K10 and HW01 BLs also downregulated the mRNA expression of leptin, but not resistin. Taken together, these results suggest that P. acidilactici BLs mediate anti-adipogenic effects by inhibiting adipogenic-related transcription factors and their target molecules.

Whey fermented by Enterococcus faecalis M157 exhibits antiinflammatory and antibiofilm activities against oral pathogenic bacteria.

The aim of the present study was to investigate the antiinflammatory and antibiofilm effects of whey fermented by Enterococcus faecalis M157 (M157-W) against oral pathogenic bacteria. The M157-W significantly inhibited IL-1ß, IL-6, and nitric oxide induced by the lipopolysaccharide of Porphyromonas gingivalis in RAW 264.7 cells. The M157-W also inhibited the production of IL-1ß and IL-8 in human periodontal ligament cells. Treatment with M157-W suppressed the phosphorylation of mitogen-activated protein kinases as well as the activation of nuclear factor-κB in RAW 264.7 cells stimulated by P. gingivalis lipopolysaccharide. Furthermore, M157-W dose-dependently inhibited Streptococcus mutans biofilm, whereas unfermented whey did not inhibit the biofilm. Treatment with M157-W significantly suppressed gtfB, gtfC, and gtfD gene expression in S. mutans compared with the control (0 µg/mL), indicating that M157-W inhibits S. mutans biofilm formation by reducing the synthesis of extracellular polymeric substances. Collectively, these results suggest that M157-W has antiinflammatory and antibiofilm activities against oral pathogenic bacteria.

Quantitative assessments of pupillary light reflexes in hospital-onset unresponsiveness.

BACKGROUND: Patients who develop hospital-onset unresponsiveness should be promptly managed in order to avoid clinical deterioration. Pupillary examination through pupillary light reflex is the gold standard method in the initial evaluation of unresponsive patients. However, the current method of shining light and subjective description often shows poor reliability. The objective of this study is to explore whether a quantitative measurement of pupillary light reflexes is useful in detecting brain herniation syndrome and predicting neurological outcomes in patients who developed hospital-onset unresponsiveness after admission for non-neurological reasons. METHODS: This was a registry-based observational study on patients who activated the neurological rapid response team at Asan Medical Center (Seoul, Korea). Hospital-onset unresponsiveness was defined as a newly developed unresponsive state as assessed by the ACDU (Alert, Confused, Drowsy, and Unresponsive) scale during the hospital stay. Demographics, comorbidities, pupillometry parameters including Neurological Pupil index, brain herniation syndrome, in-hospital mortality, and modified Rankin Scale at 3-months were analyzed. RESULTS: In 214 consecutive patients with hospital-onset unresponsiveness, 37 (17%) had brain herniation syndrome. The optimal cut-off value of Neurological Pupil index for detecting brain herniation syndrome was < 1.6 (specificity, 91% [95% confidence interval (CI) = 86-95]; sensitivity, 49% [95% CI = 32-66]). The in-hospital mortality rate was 28% (59/214); the Neurological Pupil index was negatively associated with in-hospital mortality after adjustments for the presence of brain herniation syndrome (adjusted odds ratio = 0.77, 95% CI = 0.62-0.96). Poor neurological outcomes (modified Rankin Scale ≥4) at 3 months was observed in 76% (152/201) of the patients; the Neurological Pupil index was negatively associated with poor neurological outcomes after adjustments for clinical variables (adjusted odds ratio = 0.67, 95% CI = 0.49-0.90). CONCLUSIONS: Quantitative measurements of pupillary light reflexes may be useful for early detection of potentially life-threatening neurological conditions in patients with hospital-onset unresponsiveness.

Bacteriocin-Like Inhibitory Substance (BLIS) Activity of Enterococcus faecium DB1 Against Biofilm Formation by Clostridium perfringens.

The antibiofilm effect of bacteriocin-like inhibitory substance (BLIS) from Enterococcus faecium DB1 against Clostridium perfringens was investigated in the present study. BLIS of E. faecium DB1 significantly reduced biofilm formation by C. perfringens in a dose-dependent manner for 24 and 48 h. In particular, treatment with BLIS of E. faecium DB1 significantly inhibited biofilm formation by C. perfringens on chicken meat and stainless steel coupon surfaces. Moreover, BLIS of E. faecium DB1 decreased the viability of C. perfringens biofilm and planktonic cells, indicating that the reduction of biofilm formation by C. perfringens might be achieved by killing the bacterial cells. Taken together, the present results suggest that BLIS of E. faecium DB1 can be a promising antibiofilm agent to eradicate C. perfringens.

Neurological Emergencies in Patients Hospitalized With Nonneurological Illness.

OBJECTIVE: We aimed to present neurological profiles and clinical outcomes of patients with acute neurological symptoms, which developed during hospitalization with nonneurological illness. METHODS: We organized the neurological alert team (NAT), a neurological rapid response team, to manage in-hospital neurological emergencies. In this registry-based study, we analyzed the clinical profiles and outcomes of patients who were consulted to the NAT. We also compared the 3-month mortality of patients with acute neurological symptoms with that of patients without acute neurological symptoms. RESULTS: Among the 85,507 adult patients, 591 (0.7%) activated the NAT. The most common reason for NAT activation was stroke symptoms (37.6%), followed by seizures (28.6%), and sudden unresponsiveness (24.0%). The most common diagnosis by the NAT neurologists was metabolic encephalopathy (45.5%), followed by ischemic stroke (21.2%) and seizures or status epilepticus (21.0%). Patients with NAT activation had high rates in mortality before hospital discharge (22.5%) and at 3 months (34.7%), transfer to intensive care units (39.6%), and length of hospital stay (43.1 ± 57.1 days). They also had high prevalence of poor functional status (78.1%) and recurrence of neurological symptoms at 3 months (27.2%). In a Cox proportional hazards model, patients with in-hospital neurological emergencies had a hazard ratio of 13.2 in terms of mortality at 3 months (95% confidence interval, 11.5-15.3; P < 0.001). CONCLUSIONS: Occurrence of acute neurological symptoms during hospital admission was associated with high rate of mortality and poor functional status. These results call for enhanced awareness and hospital-wide strategies for managing in-hospital neurological emergencies.

Magnetic Resonance Imaging in Neurocritically Ill Patients: Who Fails and How?

OBJECTIVES: Performing magnetic resonance imaging (MRI) in neurocritically ill patients is challenging because it often requires sedation and withholding care in the neurological intensive care unit. This study investigated the incidence of and reasons for failed or complicated MRI (MRI-FC) in such patients. METHODS: A consecutive series of 218 neurocritically ill patients who underwent brain MRI were retrospectively evaluated. Failed or complicated MRI included failure to obtain all ordered sequences, unscheduled sedative administration, decrease in oxygen saturation to less than 90%, hypotension (≥40-mm Hg decrease and/or use of inotropic agents), and cardiac or respiratory arrest. RESULTS: Failed or complicated MRI occurred in 66 patients (30.3%) and included failure to obtain MRI sequences (n = 13), unscheduled use of sedatives (n = 62), oxygen desaturation (n = 9), and hypotension (n = 6). Cardiac or respiratory arrest did not occur. Use of sedative agents while in intensive care (P < 0.01), high Acute Physiology and Chronic Health Evaluation II score (P = 0.031), and low Glasgow Coma Scale score on admission (P = 0.047) were associated with MRI-FC. Scan times were longer (P = 0.004) and Glasgow Coma Scale (P < 0.001) and Richmond Agitation Sedation Scale (P = 0.003) scores were lower (P = 0.004) after imaging in patients with MRI-FC. Previous use of sedative agents was independently associated with MRI-FC (adjusted odds ratio = 3.57, 95% confidence interval = 1.78 to 7.24, P < 0.001). CONCLUSIONS: Failed or complicated MRI was common and was associated with the use of sedative agents, severity of illness, and lower level of consciousness. Studies to ensure effective and safe performance of MRI in neurocritically ill patients are needed.

Are Genetic Variants Associated with the Location of Cerebral Arterial Lesions in Stroke Patients?

BACKGROUND: Genetic variants may play a role in determining the location of cerebral atherosclerosis. We aimed to investigate the association between RNF213, MMP2, and genetic polymorphisms linked to vascular tortuosity with the location of cerebral arterial atherosclerosis. METHODS: A prospective case-control study was conducted on patients with ischemic stroke and age- and sex-matched stroke-free controls. The stroke patients were categorized into those with intracranial artery atherosclerosis (ICAS), extracranial artery atherosclerosis (ECAS), and small vessel occlusion (SVO). Six single nucleotide polymorphisms (SNPs) including rs2118181 (FBN1), rs2179357 (SLC2A10), rs1036095 (TGFBR2), rs243865 (MMP2), rs1800470 (TGFB1), and rs112735431 (RNF213) were analyzed with the TaqMan Genotyping Assay, and the distribution of genotypes across groups was compared. RESULTS: None of the 6 SNPs were associated with stroke on comparing the 449 stroke patients (71 with ECAS, 169 with ICAS, and 209 with SVO) to the 447 controls. In the subgroup analysis, the adjusted odds ratios (aORs) for age and sex indicated a significant association between rs112735431 and ICAS in the allele comparison analysis and in the additive and dominant model analyses. rs112735431 was associated with anterior circulation involvement and increased burden of cerebral atherosclerosis. rs2179357 was significantly associated with ICAS in the recessive model analysis, and rs1800470 was significantly associated with ECAS in the recessive model analysis when compared to controls. CONCLUSION: rs112735431 was associated with ICAS and increased atherosclerosis burden in Korean stroke patients. Further studies are needed to elucidate the role of rs112735431 and to confirm the association of rs2179357 and rs1800470 with cerebral atherosclerosis.

Machine Learning Approach to Identify Stroke Within 4.5 Hours.

Background and Purpose- We aimed to investigate the ability of machine learning (ML) techniques analyzing diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging to identify patients within the recommended time window for thrombolysis. Methods- We analyzed DWI and FLAIR images of consecutive patients with acute ischemic stroke within 24 hours of clear symptom onset by applying automatic image processing approaches. These processes included infarct segmentation, DWI, and FLAIR imaging registration and image feature extraction. A total of 89 vector features from each image sequence were captured and used in the ML. Three ML models were developed to estimate stroke onset time for binary classification (≤4.5 hours): logistic regression, support vector machine, and random forest. To evaluate the performance of ML models, the sensitivity and specificity for identifying patients within 4.5 hours were compared with the sensitivity and specificity of human readings of DWI-FLAIR mismatch. Results- Data from a total of 355 patients were analyzed. DWI-FLAIR mismatch from human readings identified patients within 4.5 hours of symptom onset with 48.5% sensitivity and 91.3% specificity. ML algorithms had significantly greater sensitivities than human readers (75.8% for logistic regression, P=0.020; 72.7% for support vector machine, P=0.033; 75.8% for random forest, P=0.013) in detecting patients within 4.5 hours, but their specificities were comparable (82.6% for logistic regression, P=0.157; 82.6% for support vector machine, P=0.157; 82.6% for random forest, P=0.157). Conclusions- ML algorithms using multiple magnetic resonance imaging features were feasible even more sensitive than human readings in identifying patients with stroke within the time window for acute thrombolysis.

Combination of Dexmedetomidine and Ketamine for Magnetic Resonance Imaging Sedation.

Objectives: The use of dexmedetomidine and ketamine (DEX-KET) combination for magnetic resonance imaging (MRI) sedation has not been evaluated. We investigated the efficacy and safety of DEX-KET for sedation of patients undergoing MRI of the brain. Methods: This quasi-experimental study was conducted to compare the DEX-KET combination and midazolam for MRI sedation. We included 72 patients undergoing brain MRI following bolus injection of midazolam or DEX-KET. In August 1, 2016 a new MRI sedation protocol was implemented. After protocol implementation, bolus doses of DEX-KET were administered (DEX-KET group). Thirty-six patients from the MIDA group and 36 patients from the DEX-KET group underwent MRI sequences and were compared regarding the MRI scan time and sedation-related complications (desaturation, hypotension, cardiorespiratory arrest, and aspiration pneumonia). Results: All MRI sequences were completed for 30 patients (83.3%) from the MIDA group and for 33 patients (91.7%) from the DEX-KET group (P = 0.476). The median MRI scan time was 100.0 min (interquartile range, 87.0-111.5 min) in the MIDA group and 53.5 min (interquartile range, 45.0-60.5 min) in the DEX-KET group (P < 0.001). Complications occurred in 24 (66.7%) and 8 (22.2%) patients of the MIDA and DEX-KET group, respectively (P < 0.001). Conclusions: The efficacy of DEX-KET sedation was comparable to that of midazolam for MRI examination. DEX-KET was related to shorter scan time and lower occurrence of complications compared to midazolam.

Multidisciplinary Approach to Decrease In-Hospital Delay for Stroke Thrombolysis.

BACKGROUND AND PURPOSE: Decreasing the time delay for thrombolysis, including intravenous thrombolysis (IVT) with tissue plasminogen activator and intra-arterial thrombectomy (IAT), is critical for decreasing the morbidity and mortality of patients experiencing acute stroke. We aimed to decrease the in-hospital delay for both IVT and IAT through a multidisciplinary approach that is feasible 24 h/day. METHODS: We implemented the Stroke Alert Team (SAT) on May 2, 2016, which introduced hospital-initiated ambulance prenotification and reorganized in-hospital processes. We compared the patient characteristics, time for each step of the evaluation and thrombolysis, thrombolysis rate, and post-thrombolysis intracranial hemorrhage from January 2014 to August 2016. RESULTS: A total of 245 patients received thrombolysis (198 before SAT; 47 after SAT). The median door-to-CT, door-to-MRI, and door-to-laboratory times decreased to 13 min, 37.5 min, and 8 min, respectively, after SAT implementation (P<0.001). The median door-to-IVT time decreased from 46 min (interquartile range [IQR] 36-57 min) to 20.5 min (IQR 15.8-32.5 min; P<0.001). The median door-to-IAT time decreased from 156 min (IQR 124.5-212.5 min) to 86.5 min (IQR 67.5-102.3 min; P<0.001). The thrombolysis rate increased from 9.8% (198/2,012) to 15.8% (47/297; P=0.002), and the post-thrombolysis radiological intracranial hemorrhage rate decreased from 12.6% (25/198) to 2.1% (1/47; P=0.035). CONCLUSIONS: SAT significantly decreased the in-hospital delay for thrombolysis, increased thrombolysis rate, and decreased post-thrombolysis intracranial hemorrhage. Time benefits of SAT were observed for both IVT and IAT and during office hours and after-hours.

Red Blood Cell Distribution Width Is Associated with Severity of Leukoaraiosis.

Red blood cell distribution width (RDW) is one of the routine hematologic parameters reported in the complete blood count test, which has been recognized as strong prognostic marker for various medical conditions, especially cardiovascular disease. We evaluated that RDW was also associated with the leukoaraiosis; common radiological finding of brain and that has been strongly associated with risk of stroke and dementia. In the present study, we included 1006 non-stroke individuals who underwent brain MRI and routine complete blood count test including RDW. Fazekas scale was used to measure the severity of leukoaraiosis based on fluid-attenuated inversion recovery image, and the severity was dichotomized to mild-degree (Fazekas scale: 0-1) and severe-degree leukoaraiosis (Fazekas scale: 2-3). Univariate and multivariate logistic regression models were constructed to evaluate independent risk factor for severe-degree of leukoaraiosis. Mean age of 1006 subjects was 64.34 ± 9.11 year, and mean of RDW was 12.97 ± 0.86%. The severe-degree of leukoaraiosis (Fazekas scale ≥ 2) was found in 28.83%. In the multivariate logistic regression, 4th quartile of RDW (> 13.3%) were significantly associated with the presence of severe-degree of leukoaraiosis (adjusted odds ratio, 1.87; 95% confidence interval, 1.20-2.92) compared to the 1st quartile of RDW (< 12.5%). The significance was not changed after adjustments for hemoglobin and other hematologic indices. These findings suggest that RDW is independently associated with severity of leukoaraiosis.

Association between Serum Alkaline Phosphatase Level and Cerebral Small Vessel Disease.

BACKGROUND: Serum alkaline phosphatase (ALP) is a marker of vascular calcification. A high serum ALP level is associated with an increase in cardiovascular events, and predicts poor functional outcome in patients with stroke. We investigated whether serum ALP was associated with cerebral small vessel disease (cSVD) and large cerebral artery stenosis (LCAS). METHODS: We evaluated vascular risk factors, brain magnetic resonance images (MRIs), and MR angiograms from 1,011 neurologically healthy participants. The presence of silent lacunar infarction (SLI) and moderate-to-severe cerebral white matter hyperintensities (MS-cWMH) were evaluated as indices of cSVD on brain MRIs. Findings of extracranial arterial stenosis (ECAS) or intracranial arterial stenosis (ICAS) were considered to be indices of LCAS on MR angiograms. RESULTS: Subjects with SLI (odds ratio [OR]: 2.09; 95% confidence interval [CI]: 1.27-3.42; p = 0.004) and MS-cWMH (OR: 1.48; 95% CI; 1.03-2.13, p = 0.036) were significantly more likely to have ALP levels in the third tertile (ALP ≥ 195 IU/L) than the first tertile (ALP ≤ 155 IU/L), after adjusting for cardiovascular risk factors. The mean serum ALP level was significantly higher in patients with SLI or MS-cWMH compared to patients without those findings. After adjustment for confounding factors, the multivariate model found that the statistical significance of serum ALP remained when the presence of SLI (OR: 1.05 per 10 IU/L increase in ALP; 95% CI: 1.02-1.08; p = 0.003) or MS-cWMH (OR: 1.03 per 10 IU/L increase in ALP; 95% CI: 1.00-1.06; p = 0.025) were added to the model. There were no differences in the proportions of patients with LCAS, ICAS, and ECAS across the serum ALP tertiles. CONCLUSIONS: Our study of neurologically healthy participants found a positive association between serum ALP level and indicators of cSVD, but no association between serum ALP level and the indicators of LCAS.

Mice lacking MKP-1 and MKP-5 Reveal Hierarchical Regulation of Regenerative Myogenesis.

The relative contribution of the MAP kinase phosphatases (MKPs) in the integration of MAP kinase-dependent signaling during regenerative myogenesis has yet to be fully investigated. MKP-1 and MKP-5 maintain skeletal muscle homeostasis by providing positive and negative effects on regenerative myogenesis, respectively. In order to define the hierarchical contributions of MKP-1 and MKP-5 in the regulation of regenerative myogenesis we genetically ablated both MKPs in mice. MKP-1/MKP 5-deficient double-knockout (MKP1/5- DKO) mice were viable, and upon skeletal muscle injury, were severely impaired in their capacity to regenerate skeletal muscle. Satellite cells were fewer in number in MKP1/5-DKO mice and displayed a reduced proliferative capacity as compared with those derived from wild-type mice. MKP1/5-DKO mice exhibited increased inflammation and the macrophage M1 to M2 transition during the resolution of inflammation was impaired following injury. These results demonstrate that the actions of MKP-1 to positively regulate myogenesis predominate over those of MKP-5, which negatively regulates myogenesis. Hence, MKP-1 and MKP-5 function to maintain skeletal muscle homeostasis through non-overlapping and opposing signaling pathways.

Blood genomic profiling in extracranial- and intracranial atherosclerosis in ischemic stroke patients.

OBJECTIVE: Extracranial- and intracranial atherosclerosis (ECAS and ICAS) have been suggested to have different pathogeneses. Blood genomic profiling may identify their unique molecular signatures. METHODS: Whole gene microarray of peripheral blood was performed in 24 patients with acute ischemic stroke (ECAS, n=12; ICAS, n=12) and 12 healthy controls. Differential gene expression and gene set enrichment analysis (GSEA) were conducted. Plasma resistin levels were compared across independent samples of stroke patients with ECAS (n=39), ICAS (n=20), and small vessel disease (SVD, n=57). RESULTS: Microarray revealed that 144 and 24 transcripts were altered in ECAS and ICAS, respectively, compared to controls. All the transcripts that were differentially expressed in ICAS were also differentially expressed in ECAS. A total of 120 transcripts were differentially expressed only in ECAS. Gene sets related to immune response and protein metabolism were altered in both ECAS and ICAS, but the magnitude of gene alteration was higher in ECAS than in ICAS. Several genes of interest including RETN, IRF5, CD163, and CHST13 were more highly expressed in ECAS than in ICAS. Circulating resistin levels were elevated in independent samples of ECAS, but not in those of ICAS, compared to those of SVDs. CONCLUSIONS: ECAS showed prominent genomic alteration related to immune response compared to ICAS. Although there was no ECAS-specific gene to be identified on microarray, the level of resistin expression was high on peripheral blood in ECAS, suggesting that resistin is associated with the pathogenesis of ECAS.