Two Decades of Brain Tumour Imaging with O-(2-[18F]fluoroethyl)-L-tyrosine PET: The Forschungszentrum Jülich Experience.

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Differential neural structures, intrinsic functional connectivity, and episodic memory in subjective cognitive decline and healthy controls.

The neural correlates of subjective cognitive decline (SCD; i.e., without objectifiable deficit) remain to be elucidated. Possible causes of SCD include early neurodegeneration related to Alzheimer's disease or functional and structural changes related to sub-clinical depression. We investigated the relationship between episodic memory performance or memory complaints and structural or functional magnetic resonance imaging (MRI) measures in participants with SCD (n=18) but without psychiatric disorders and healthy controls (n=31). In SCD, memory complaints were not associated with memory performance but with sub-clinical depression and executive functions. SCD-associated memory complaints correlated with higher amygdala and parahippocampal gyrus (specifically subiculum) gray matter density. In controls, but not in SCD, mesiotemporal gray matter density and superior frontal gyrus functional connectivity predicted memory performance. In contrast, in SCD, only a trend toward a correlation between memory performance and gray matter density in the parietooccipital lobes was observed. In our memory-clinic sample of SCD, we did not observe incipient neurodegeneration (limited to structural and functional MRI) but rather sub-clinical depression underlying subjective cognitive complaints.

Fasting plasma glucose variability in midlife and risk of Parkinson's disease: A nationwide population-based study.

AIM: Despite the recognized association between type 2 diabetes (T2D) and Parkinson's disease (PD), the implications of glycaemic variability for patients with PD are as yet unknown. For this reason, our study assessed the future risk of incident PD according to visit-to-visit fasting plasma glucose (FPG) variability, as calculated by standard deviation (FPG-SD), coefficient variance (FPG-CV) and variability independent of the mean (FPG-VIM). METHODS: Using the Korean National Health Insurance Service Health Screening Cohort, 131,625 Korean adults without diabetes were followed. They were divided into a midlife group (age<65 years) and an elderly group (age≥65 years) throughout a median follow-up of 8.4 years. RESULTS: Adjusted hazard ratios (HRs) were calculated using multivariable Cox proportional-hazards analysis. In the midlife group, HRs for incident PD in the highest quartile of FPG variability (as measured by SD, CV and VIM) were 1.37 [95% confidence interval (CI): 1.09-1.73], 1.33 (95% CI: 1.06-1.68) and 1.35 (95% CI: 1.07-1.70), respectively, vs the lowest variability quartile group. However, while incident PD did not differ according to FPG variability in the elderly group, Kaplan-Meier curves of PD probability in the midlife group showed a progressively increasing risk of PD the higher the FPG variability. According to a multivariable adjusted model, every 1-SD unit increment in glycaemic variability was associated with a 9% higher risk of incident PD in the midlife group. CONCLUSION: Increased long-term glycaemic variability may be a precipitating risk factor for developing PD in the midlife population without diabetes.

Factors Affecting Microbiological Quality of Vegetable- and Meat-Based Meals Served at Cafeterias in the Republic of Korea.

A total of 364 samples of vegetable- and meat-based meals were collected at three processing steps: step I, preparation of raw ingredients; step II, processing and cooking; and step III, finished meals. Microbiological quality was evaluated by using data for the prevalence and concentration of the aerobic plate counts, total coliforms (TC), fecal coliforms (FC), and Escherichia coli. The data were analyzed for differences between cafeterias, seasons, raw materials, and processing steps. Fourteen (15.2%) of the 92 finished meal samples were microbiologically unsatisfactory. Neither cafeteria nor season was significantly associated with microbiological quality ( P > 0.05). However, the type of raw ingredients and processing steps were significantly associated with differences in microbiological quality. Vegetable-based meals had higher TC concentrations than meat-based meals because salad and seasoned and fermented vegetables are not cooked, unlike heat-processed meat products. Microbial counts tended to decrease through the processing steps, and E. coli, which could only be enumerated on uncooked chicken breast (1.6 log CFU/g) and sliced pork (2.6 log CFU/g), was totally eliminated by boiling and roasting. However, the presence of FC was not completely eliminated, even by cooking, and so this group of organisms should be considered as an important indicator of hygienic meal preparation in cafeterias. Although pathogenic E. coli was not isolated in this study, continuous microbiological monitoring of composite foods served in cafeterias should be performed as the presence of TC and FC in finished meals indicates the potential for contamination by pathogenic E. coli.

Dipeptidyl peptidase-4 inhibitor use and risk of diabetic retinopathy: A population-based study.

AIMS: This study examined whether dipeptidyl peptidase (DPP)-4 inhibitor use is beneficial or harmful to diabetic retinopathy (DR) compared with other glucose-lowering agents in patients with type 2 diabetes (T2D). METHODS: From a population-based cohort provided by the National Health Insurance Service in Korea, 67,743 adults with T2D were identified as having been treated with oral glucose-lowering agents between 2008 and 2013. Matching (1:1) was performed for two groups comparing ever-use (cases) and never-use (controls) of DPP-4 inhibitors (n=14,522 in each group). Cox regression analyses were used to assess risk of the following DR events: vitreous haemorrhage; vitrectomy or photocoagulation; intravitreal agent use; and blindness. RESULTS: During a median follow-up of 28.4 (14.0-45.2) months, there were 305 (in controls) and 342 (in cases) composite DR events. DPP-4 inhibitor ever-use was not associated with overall risk of composite DR events [adjusted hazard ratio (HR): 1.08, 95% CI: 0.93-1.26] compared with never-use, nor was the risk of each DR outcome increased with DPP-4 inhibitor therapy either. However, DPP-4 inhibitor administration for<12 months was associated with a greater risk of composite DR events (adjusted HR: 1.31, 95% CI: 1.09-1.57) compared with other glucose-lowering agents over the same treatment period. CONCLUSION: In comparison to other oral glucose-lowering agents, DPP-4 inhibitor treatment did not increase overall risk of DR. However, DPP-4 inhibitors may be associated with an increased risk of retinopathy events early in the treatment phase.

Geriatric oral and maxillofacial dysfunctions in the context of geriatric syndrome.

OBJECTIVES: To propose the application of the concept of geriatric syndrome for common geriatric oral and maxillofacial dysfunctions and to suggest the necessity of developing effective evaluation methods for oral and maxillofacial frailty. DESIGN: The concepts of frailty and geriatric syndrome based on multi-morbidity and polypharmacy were applied to five common geriatric oral medicinal dysfunctional problems: salivary gland hypofunction (dry mouth), chronic oral mucosal pain disorders (burning mouth symptoms), taste disorders (taste disturbances), swallowing disorders (dysphagia), and oral and maxillofacial movement disorders (oromandibular dyskinesia and dystonia). RESULTS: Each of the dysfunctions is caused by various kinds of diseases and/or conditions and medications, thus the concept of geriatric syndrome could be applied. These dysfunctions, suggested as components of oral and maxillofacial geriatric syndrome, are associated and interacted with each other in a complexity of vicious cycle. The resulting functional impairments caused by this syndrome can cause oral and maxillofacial frailty. CONCLUSIONS: Geriatric oral and maxillofacial dysfunctions could be better appreciated in the context of geriatric syndrome. The development of effective methods for evaluating the severity of these dysfunctions and the resulting frailty is essential.

Functional Disintegration of the Default Mode Network in Prodromal Alzheimer's Disease.

Neurodegenerative brain changes can affect the functional connectivity strength between nodes of the default-mode network (DMN), which may underlie changes in cognitive performance. It remains unclear how the functional connectivity strength of DMN nodes differs from healthy to pathological aging and whether these changes are cognitively relevant. We used resting-state functional magnetic resonance imaging to investigate the functional connectivity strength across five DMN nodes in 25 healthy controls (HC), 28 subjective cognitive decline (SCD) participants, and 25 prodromal Alzheimer's disease (AD) patients. After identifying the ventral medial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), retrosplenial cortex (RSC), inferior parietal lobule, and the hippocampus we investigated the functional strength between DMN nodes using temporal network modeling. Functional coupling of the vmPFC and PCC in prodromal AD patients was disrupted. This vmPFC-PCC coupling correlated positively with memory performance in prodromal AD. Furthermore, the hippocampus de-coupled from posterior DMN nodes in SCD and prodromal AD patients. There was no coupling between the hippocampus and the anterior DMN. Additional mediation analyses indicated that the RSC enables communication between the hippocampus and DMN regions in HC but none of the other two groups. These results suggest an anterior-posterior disconnection and a hippocampal de-coupling from posterior DMN nodes with disease progression. Hippocampal de-coupling already occurring in SCD may provide valuable information for the development of a functional biomarker.

Continuous ohmic heating of commercially processed apple juice using five sequential electric fields results in rapid inactivation of Alicyclobacillus acidoterrestris spores.

Spores of Alicyclobacillus acidoterrestris, a spoilage bacterium, cause problems for the apple juice industry because they are resistant to thermal treatment. Here, we examined the sporicidal effect of an ohmic heating (OH) system with five sequential electric fields and compared it with that of conventional heating. Apple juice product (50kg) inoculated with A. acidoterrestris spores were subjected to OH (electric field strength=26.7V/cm; frequency=25kHz) at 85-100°C for 30-90s. The effect of conventional heating was also examined under these conditions. OH treatment at 100°C for 30s resulted in total inactivation of the inoculum, with no recovery of viable cells (initial population=4.8-4.9logCFU/ml), whereas 3.6-4.9logCFU/ml of the spores survived conventional heating. OH did not alter the quality (°Brix, color, and pH) of commercial apple juice (p>0.05). These results suggest that the OH system is superior to conventional heating for rapid sterilization (30s) of apple juice to assure microbiological quality in the absence of chemical additives.

Complete mitochondrial genome of the Amur hedgehog Erinaceus amurensis (Erinaceidae) and higher phylogeny of the family Erinaceidae.

We sequenced and characterized the complete mitogenome (KX964606) of the Amur hedgehog Erinaceus amurensis to provide more data for comparative mitogenomics of the genus Erinaceus (Erinaceidae). The mitogenome of E. amurensis is a circular molecule 16,941 bp long, consisting of a control region and a conserved set of 37 genes containing 13 protein-coding genes, 22 tRNA genes, and two rRNA genes (12S rRNA and 16S rRNA). The mitogenome of E. amurensis is AT-biased, with a nucleotide composition of 33.9% A, 21.1% C, 32.6% T, and 12.4% G. The mitogenomes of E. amurensis and the closely related hedgehog species E. europaeus, excluding the control region (66.7%), share over 90% sequence similarity. According to the inter-generic relationship based on six mitogenomes described from five genera of Erinaceidae, the subfamilies Erinaceinae and Galericinae are strongly supported as monophyletic groups, with each genus well placed within its own subfamily. Within the subfamily Erinaceinae, E. amurensis is a sister species to E. europaeus, and the relationship between Hemiechinus and Erinaceus is strongly supported. Within the subfamily Galericinae, the clade of Hylomys + Neotetracus was sister to that of Echinosorex, with clades supported by high values. Our findings will help to understand the codon usage pattern and molecular evolution of E. amurensis, and provide insight into inter-generic relationships within the family Erinaceidae. In future studies, the inclusion of mitogenomes from other genera would greatly enhance our understanding of higher phylogeny within the Erinaceidae.

Activities of daily living and oral hygiene status of older Korean patients in a long-term care facility.

OBJECTIVES: This study investigated the relationship between oral hygiene conditions, activities of daily living (ADL) and cognitive ability in older Korean patients in long-term care facilities. METHODS: Ninety older persons (65+) were randomly sampled from a possible 112 residents in a single facility. They participated in a 2-month-long survey. The Korean Modified Barthel Index was used to measure the ADL, and cognitive ability was measured using the Mini-Mental State Examination, Korean version. Oral hygiene status was measured using the Simplified Oral Hygiene Index and the Tongue Coating Index (TCI). RESULTS: Older participants with complete dependence manifested significantly poorer oral hygiene (P < 0.05). Scores on the TCI were significantly higher in participants who were dentulous with partial dependence (P < 0.05). A multiple regression analysis showed that dependence and being dentulous significantly predicted poorer oral hygiene (P < 0.05). CONCLUSIONS: This study suggests that older participants with complete dependence had poor oral hygiene on tooth surfaces, while participants with partial dependence had poor tongue hygiene. In addition, dentulous older participants had poorer tongue hygiene than edentulous ones. This indicates the need to assess tooth status and provide oral care services via ADL in long-term care facilities.

Interferon-inducible T-cell alpha chemoattractant (ITAC) induces the melanocytic migration and hypopigmentation through destabilizing p53 via histone deacetylase 5: a possible role of ITAC in pigment-related disorders.

BACKGROUND: Cell migration plays a major role in the immune response and in tumorigenesis. Interferon-inducible T-cell alpha chemoattractant (ITAC) elicits a strong chemotactic response from immune cells. OBJECTIVES: To examine the effect of ITAC on melanocyte migration and pigmentation and its involvement in related disorders, and to investigate potential key players in these processes. METHODS: Human melanocytes or melanoma cells were treated with ITAC and a migration assay was carried out. Global gene expression analysis was performed to find genes regulated by ITAC treatment. The function of key players involved in ITAC-induced cellular processes was addressed using knockdown or overexpression experiments in combination with ITAC treatment. ITAC expression in the inflammation-associated hypopigmentary disorder, vitiligo, was examined. RESULTS: Among CXCR3 ligands, only ITAC induced melanocyte migration. ITAC treatment upregulated the expression of histone deacetylase 5 (HDAC5) and downregulated that of p53, a known target of HDAC5. Through knockdown or overexpression of HDAC5 and p53, we confirmed that HDAC5 mediates ITAC-induced migration by decreasing levels of p53 via deacetylation. In addition, ITAC treatment could decrease pigmentation in a p53- and HDAC5-dependent manner. Finally, the increased migration of human melanoma cells by ITAC treatment and the increased ITAC expression in the epidermis of vitiligo skin were verified. CONCLUSIONS: This study provides in vitro evidence for the migratory and hypopigmentation effects of ITAC on melanocytic cells, gives translational insights into the roles of ITAC in pathological conditions, and suggests that HDAC5 and its substrate p53 are potent targets for regulating ITAC-induced cellular processes.

Survival of foodborne pathogens (Escherichia coli O157:H7, Salmonella Typhimurium, Staphylococcus aureus, Listeria monocytogenes, and Vibrio parahaemolyticus) in raw ready-to-eat crab marinated in soy sauce.

Knowing the survival characteristics of foodborne pathogens in raw ready-to-eat (RTE) seafood is the key to predicting whether they pose a microbiological hazard. The present study examined the survival of Escherichia coli O157:H7, Salmonella Typhimurium, Vibrio parahaemoliticus, Listeria monocytogenes, and Staphylococcus aureus in raw RTE crab marinated in soy sauce. Inoculated crabs (initial bacterial population=4.1-4.4logCFU/g) were immersed in soy sauce and then stored at refrigeration (5°C) or room temperature (22°C) for up to 28days. At 5°C, all bacteria (except V. parahaemolyticus) survived in crab samples until Day 28 (counts of 1.4, 1.6, 3.1, 3.2 log CFU/g for E. coli O157:H7, S. Typhimurium, L. monocytogenes, and S. aureus, respectively). However, at 22°C, all tested bacteria were more susceptible to the antimicrobial effects of marination. Regardless of temperature, foodborne pathogens attached to crab samples were more resistant to marination than those suspended in soy sauce samples; however, the survival pattern for each species was different. Gram-positive bacteria were most resistant to marination conditions (high salinity, low pH), whereas V. parahaemolyticus was extremely susceptible. Marination is the only antibacterial step in the manufacturing processes; however, the results presented herein reveal that this is not sufficient to inactivate foodborne pathogens. In particular, the survival of pathogens on crabs at refrigeration temperature may pose a major hazard for the consumption of raw RTE seafood. Thus, appropriate decontamination methods and implementation of safety management practices are needed. This study provides predictive microbiological information of foodborne pathogens in raw RTE seafood with marination.

Aberrant functional connectivity differentiates retrosplenial cortex from posterior cingulate cortex in prodromal Alzheimer's disease.

The posterior cingulate cortex (PCC) is a key hub of the default mode network, a resting-state network involved in episodic memory, showing functional connectivity (FC) changes in Alzheimer's disease (AD). However, PCC is a cytoarchitectonically heterogeneous region. Specifically, the retrosplenial cortex (RSC), often subsumed under the PCC, is an area functionally and microanatomically distinct from PCC. To investigate FC patterns of RSC and PCC separately, we used resting-state functional magnetic resonance imaging in healthy aging participants, patients with subjective cognitive impairment, and prodromal AD. Compared to the other 2 groups, we found higher FC from RSC to frontal cortex in subjective cognitive impairment but higher FC to occipital cortex in prodromal AD. Conversely, FC from PCC to the lingual gyrus was higher in prodromal AD. Furthermore, data indicate that RSC and PCC are characterized by differential FC patterns represented by hub-specific interactions with memory and attentions scores in prodromal AD compared to cognitively normal individuals, possibly reflecting compensatory mechanisms for RSC and neurodegenerative processes for PCC. Data thus confirm and extend previous studies suggesting that the RSC is functionally distinct from PCC.

Illness versus substance use effects on the frontal white matter in early phase schizophrenia: A 4Tesla (1)H-MRS study.

OBJECTIVE: Young adults with early phase schizophrenia often report a past or current pattern of illicit substance use and/or alcohol misuse. Still, little is known about the cumulative and separate effects of each stressor on white matter tissue, at this vulnerable period of brain development. METHODS: Participants involved 24 healthy controls with a past or current history of sustained illicit drug use and/or alcohol misuse (users), 23 healthy controls without such history (normative data), and 27 users with early phase schizophrenia. (1)H-MRS data were acquired from a large frontal volume encompassing 95% of white matter, using a 4Tesla scanner (LASER sequence, TR/TE 3200/46ms). RESULTS: Reduced levels of choline-containing compounds (Cho) were specific to the effect of illness (Cohen's d=0.68), with 22% of the variance in Cho levels accounted for by duration of illness. Reduced levels of myoInositol (d=1.10) and creatine plus phosphocreatine (d=1.07) were specific to the effects of illness plus substance use. Effect of substance use on its own was revealed by reductions in levels of glutamate plus glutamine (d=0.83) in control users relative to normative data. CONCLUSIONS: The specific effect of illness on white matter might indicate a decreased synthesis of membrane phospholipids or alternatively, reduced membrane cellular density. In terms of limitations, this study did not include patients without a lifetime history of substance use (non-users), and the specific effect of each substance used could not be studied separately.

Destruction of Bacillus cereus spores in a thick soy bean paste (doenjang) by continuous ohmic heating with five sequential electrodes.

UNLABELLED: This study selected spores from Bacillus cereus FSP-2 strain (the isolate from a commercial doenjang processing line) as the test strain which showed significantly higher thermal resistance (P < 0·05) than B. cereus reference strain (ATCC 27348). The spores in doenjang were subjected to ohmic heating (OH) at 95, 105, 115 and 125°C for 30, 60 or 90 s using a five sequential electrode system (electrical field: 26·7 V cm(-1) ; alternating current frequency: 25 kHz). OH at 105°C for 30-90 s reduced the B. cereus spore count in doenjang samples to <4 log CFU g(-1) . Since OH treatment at 115 and 125°C caused a perceivable colour change in the product (>1·5 National Bureau of Standards units), treatment at 105°C for 60 s was selected and applied on a large scale (500 kg of product). Reliable and reproducible destruction of B. cereus spores occurred; the reductions achieved (to < 4 log CFU g(-1) ) met the Korean national standards. Scanning electron microscopy revealed microstructural alterations in the spores (shrinkage and a distorted outer spore coat). OH is an effective method for destroying B. cereus spores to ensure the microbiological quality and safety of a thick, highly viscous sauce. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that an ohmic heating (OH) using a five sequential electrode system can effectively destroy highly heat-resistant Bacillus cereus spores which have been frequently found in a commercial doenjang processing line without perceivable quality change in the product. In addition, it may demonstrate high potential of the unique OH system used in this study that will further contribute to ensure microbiological quality and safety of crude sauces containing high levels of electrolyte other than doenjang as well.

Effects of low-fat milk consumption on metabolic and atherogenic biomarkers in Korean adults with the metabolic syndrome: a randomised controlled trial.

BACKGROUND: Previous studies of the health effects of low-fat milk or dairy consumption on the metabolic syndrome have yielded inconsistent results. The present study aimed to investigate the effects of low-fat milk consumption on traits associated with the metabolic syndrome, as well as inflammatory and atherogenic biomarkers, in Korean adults with the metabolic syndrome. METHODS: Overweight Koreans with the metabolic syndrome (n = 58) were recruited and randomly assigned to either the low-fat milk or control group. The low-fat milk group was instructed to consume two packs of low-fat milk per day (200 mL twice daily) for 6 weeks, and the control group was instructed to maintain their habitual diet. Clinical investigations were conducted during the screening visit, on study day 0, and after 6 weeks. RESULTS: No significant differences in changes in body mass index, blood pressure, lipid profile and adiponectin levels, as well as levels of inflammatory markers, oxidative stress markers and atherogenic markers, were found between the low-fat milk and control groups. However, compared to the controls, significant favourable decreases in serum soluble vascular adhesion molecule-1 and endothelin-1 levels were found in the 12 subjects with high blood pressure and in the 18 subjects with hypertriglyceridaemia in the low-fat milk group. CONCLUSIONS: The present study did not demonstrate an overall beneficial effect of low-fat milk consumption in subjects with the metabolic syndrome. However, low-fat milk consumption may have a favourable effect on atherogenic markers in subjects with high blood pressure or hypertriglyceridaemia.

Inactivation of Bacillus cereus spores in a tsuyu sauce using continuous ohmic heating with five sequential elbow-type electrodes.

AIMS: The effect of ohmic heating (OH) in a pilot plant system which had a zig-zag shaped (elbow-type) ohmic heater with five sequential voltage electrodes was investigated on Bacillus cereus spores in a commercial tsuyu sauce. METHODS AND RESULTS: The electrical field was fixed at 26·7 V cm(-1) with an alternating current frequency of 25 kHz. Raw tsuyu sauce (50 l) inoculated with B. cereus spores was submitted in a 4 × 3 factorial design to the OH system and heated at 95, 105, 115, and 125°C each for 30, 60, and 90 s. Survival of B. cereus spores and colour change in the commercial tsuyu sauce were both measured before and after treatment. As the treatment temperature and time increased, the number of surviving B. cereus spores decreased. The OH treatment in a bath-type process at 105°C for more than 30 s resulted in the total inactivation of the inoculated B. cereus spores (average 5·4 log reductions to undetectable levels after treatment). The OH protocol of heating at 105°C for 60 s which ensure complete eradication of the inoculated spores without compromising product quality was chosen and investigated for its suitability for commercial application on bulk quantities of samples (500 l). Reliable and reproducible reductions in B. cereus spore counts of 4·7-5·5 log CFU ml(-1) (mean ± standard deviation = 5·1 ± 0·3 CFU ml(-1) ) were achieved by the selected protocol of the continuous OH treatment (105°C for 60 s). CONCLUSION: This study suggests that OH treatment with five sequential elbow-type electrodes has great potential as an industrial sterilizing method for liquid food contaminated with B. cereus spores. SIGNIFICANCE AND IMPACT OF THE STUDY: This procedure will enhance the microbiological quality of liquid foods while minimizing quality deterioration.

Changes in the Microbial Composition of Microbrewed Beer during the Process in the Actual Manufacturing Line.

This study investigated changes in the microbial composition of microbrewed beer during the manufacturing processes and identified potential microbial hazards, effective critical quality control points, and potential contamination routes. Comprehensive quantitative (aerobic plate count, lactic acid bacteria, fungi, acetic acid bacteria, coliforms, and Bacillus cereus) and qualitative (Escherichia coli and eight foodborne pathogens) microbiological analyses were performed using samples of raw materials (malt and manufacturing water), semiprocessed products (saccharified wort, boiled wort, and samples taken during the fermentation and maturation process), and the final product obtained from three plants. The initial aerobic plate count and lactic acid bacteria counts in malt were 5.2 and 4.3 log CFU/g, respectively. These counts were reduced to undetectable levels by boiling but were present at 2.9 and 0.9 log CFU/ml in the final product. Fungi were initially present at 3.6 log CFU/g, although again, the microbes were eliminated by boiling; however, the level in the final product was 4.6 log CFU/ml. No E. coli or foodborne pathogens (except B. cereus) were detected. B. cereus was detected at all stages, although it was not present in the water or boiled wort (total detection rate » 16.4%). Results suggest that boiling of the wort is an effective microbial control measure, but careful management of raw materials and implementation of effective control measures after boiling are needed to prevent contamination of the product after the boiling step. The results of this study may constitute useful and comprehensive information regarding the microbiological quality of microbrewed beer.

CD44+/CD24- Cancer Stem Cells Are Associated With Higher Grade of Canine Mammary Carcinomas.

The CD44+/CD24- phenotype identifies cancer stem cell (CSC) properties in canine mammary carcinoma (MC); however, the histopathological features associated with this phenotype remain to be elucidated. Here, we determined whether the CD44+/CD24- phenotype was associated with hormonal receptor (HR; estrogen receptor [ER] and/or progesterone receptor [PR]) status and/or triple (ER, PR, and human epithelial growth factor receptor 2)-negative (TN) subtype; conventional histological evaluation was also performed. We found that, as single markers, both CD44+ and CD24+ were associated with less aggressive histological types, low grade, and a non-TN subtype; both markers were associated with HR positivity. On the other hand, a CD44+/CD24- phenotype was associated with higher grade of carcinoma. Therefore, our results suggest that immunohistochemical phenotyping for CD44/CD24 is useful for the evaluation of tumor behavior as well as CSC-like properties in canine MCs.

Metabolic stress induces a Wnt-dependent cancer stem cell-like state transition.

Reciprocal interactions between cancer cells and the tumor microenvironment drive multiple clinically significant behaviors including dormancy, invasion, and metastasis as well as therapy resistance. These microenvironment-dependent phenotypes share typical characteristics with cancer stem cells (CSC). However, it is poorly understood how metabolic stress in the confined tumor microenvironment contributes to the emergence and maintenance of CSC-like phenotypes. Here, we demonstrate that chronic metabolic stress (CMS) in a long-term nutrient deprivation induces a Wnt-dependent phenoconversion of non-stem cancer cells toward stem-like state and this is reflected in the transcriptome analysis. Addition of Wnt3a as well as transfection of dominant-negative Tcf4 establishes an obligatory role for the Wnt pathway in the acquisition of CSC-like characteristics in response to metabolic stress. Furthermore, systematic characterization for multiple single cell-derived clones and negative enrichment of CD44+/ESA+ stem-like cancer cells, all of which recapitulate stem-like cancer characteristics, suggest stochastic adaptation rather than selection of pre-existing subclones. Finally, CMS in the tumor microenvironment can drive a CSC-like phenoconversion of non-stem cancer cells through stochastic state transition dependent on the Wnt pathway. These findings contribute to an understanding of the metabolic stress-driven dynamic transition of non-stem cancer cells to a stem-like state in the tumor metabolic microenvironment.