Brain Tissue Oxygen and BOLD fMRI Under Different Levels of Neuronal Activity.

Localized increases in neuronal activity are supported by the hemodynamic response, which delivers oxygen to the brain tissue to support synaptic functions, action potentials and other neuronal processes. However, it remains unknown if changes in baseline neuronal activity, which are expected to reflect neuronal metabolic demand, alter the relationship between the local hemodynamic and oxygen behaviour. In order to better characterize this system, we examine here the relationship between brain tissue oxygen (PO2) and hemodynamic responses (BOLD functional MRI) under different levels of neuronal activity. By comparing the stimulus-evoked responses during different levels of baseline neuronal activity, the awake state vs isoflurane anesthesia, we were able to measure how a known change in neuronal demand affected tissue PO2 as well as the hemodynamic response to stimulation. We observed a high correlation between stimulus-evoked PO2 and BOLD responses in the awake state. Moreover, we found that the evoked PO2 and BOLD responses were still present despite the elevated tissue oxygen baseline and decreased baseline of neuronal activity under low concentration isoflurane, and that the magnitudes of these responses decreased by similar proportions but the relationship between these signals was distorted. Our findings point to distortion of the BOLD-PO2 relationship due to anesthesia. The feedback mechanism to adjust the level of brain tissue oxygen, as well as the correlation between BOLD and PO2 responses, are impaired even by a small dose of anesthetics.

Factors associated with the contemplative stage of readiness to initiate osteoporosis treatment.

We investigated the factors associated with readiness for initiating osteoporosis treatment in women at high risk of fracture. We found that women in the contemplative stage were more likely to report previously being told having osteoporosis or osteopenia, acknowledge concern about osteoporosis, and disclose prior osteoporosis treatment. INTRODUCTION: Understanding factors associated with reaching the contemplative stage of readiness to initiate osteoporosis treatment may inform the design of behavioral interventions to improve osteoporosis treatment uptake in women at high risk for fracture. METHODS: We measured readiness to initiate osteoporosis treatment using a modified form of the Weinstein Precaution Adoption Process Model (PAPM) among 2684 women at high risk of fracture from the Activating Patients at Risk for OsteoPOroSis (APROPOS) clinical trial. Pre-contemplative participants were those who self-classified in the unaware and unengaged stages of PAPM (stages 1 and 2). Contemplative participants were those in the undecided, decided not to act, or decided to act stages of PAPM (stages 3, 4, and 5). Using multivariable logistic regression, we evaluated participant characteristics associated with levels of readiness to initiate osteoporosis treatment. RESULTS: Overall, 24% (N = 412) self-classified in the contemplative stage of readiness to initiate osteoporosis treatment. After adjusting for age, race, education, health literacy, and major osteoporotic fracture in the past 12 months, contemplative women were more likely to report previously being told they had osteoporosis or osteopenia (adjusted odds ratio [aOR] (95% CI) 11.8 (7.8-17.9) and 3.8 (2.5-5.6), respectively), acknowledge concern about osteoporosis (aOR 3.5 (2.5-4.9)), and disclose prior osteoporosis treatment (aOR 4.5 (3.3-6.3)) than women who self-classified as pre-contemplative. CONCLUSIONS: For women at high risk for future fractures, ensuring women's recognition of their diagnosis of osteoporosis/osteopenia and addressing their concerns about osteoporosis are critical components to consider when attempting to influence stage of behavior transitions in osteoporosis treatment.

Nisin incorporation enhances the inactivation of lactic acid bacteria during the acid wash step of bioethanol production from sugarcane juice.

Bioethanol fermentation is continuously exposed to contamination by Lactic Acid Bacteria (LAB). In this study, the effect of adding nisin (250 mg l-1 ) to the acid wash on the viability of five bacterial contaminants were evaluated both alone and in co-incubation with Saccharomyces cerevisiae. Additionally, fed-batch fermentation was performed using an acid or acid/nisin wash for S. cerevisiae alone and cocultured with the LAB strains. Parameters such as ethanol production, sugar consumption and lactic acid production were monitored. Four model LAB were more susceptible to the acid/nisin wash than the acid wash, and were most susceptible when incubated with yeast. A fifth model LAB was very sensitive to both treatments regardless of the presence of yeast. The addition of nisin to the acid wash lowered the required time for adequate washing and resulted in a higher ethanol production (54·5 ± 0·1 g l-1 ) than the acid wash alone (52·6 ± 0·1 g l-1 ) in a subsequent fermentation. These results indicate the potential benefits of supplementing with nisin to improve the acid wash step of bioethanol fermentations. SIGNIFICANCE AND IMPACT OF THE STUDY: Acid washing by the bioethanol fermentation industry reduces yeast efficiency and selects for contaminant bacteria that are resistant to acid treatments. This study demonstrates that the incorporation of nisin into the acid wash step results in a more potent removal of lactic acid bacteria while significantly shortening the length of time needed for the acid wash.

Invited review: Hispanic-style cheeses and their association with Listeria monocytogenes.

The rise in consumption of Hispanic-style cheeses (HSC), due in large part to the increasing Hispanic population in the United States, has not been met with advances in food safety sufficient to prevent the numerous outbreaks and recalls due to Listeria monocytogenes. Hispanic-style cheeses are typically high moisture and have low salt content and low acidity from being subjected to little to no ripening. These conditions necessitate refrigeration to maintain safety and quality, as the majority of traditional extrinsic preservation methods are either ineffective or disrupt the mild sensory attributes of HSC. Unfortunately, the cold-growth of L. monocytogenes presents significant problems from post-pasteurization contamination or insufficient pasteurization. In this review, we discuss the factors affecting listerial contamination and growth in HSC, and present current knowledge of L. monocytogenes incidence in manufacturing settings and commercial prevalence. Furthermore, we differentiate HSC types by processing methods to aid with interpretation of works involving nonstandardized varieties and, finally, summarize research on intervention methods for eliminating listerial contaminants in HSC.

Beyond antibiotic selection: concordance with the IDSA guidelines for uncomplicated urinary tract infections.

The purpose of this report was to evaluate concordance with the most recent guidelines for the treatment of uncomplicated UTI based on antibiotic selection, dosage, frequency, and duration. A historical review of patients' medical records at a university-based internal medicine clinic was conducted. When aggregated across antibiotic type, frequency, and duration, overall concordance was 33.96 %. Prescribing concordance for uncomplicated UTI in the local region is suboptimal.

Use of a miniature laboratory fresh cheese model for investigating antimicrobial activities.

Hispanic-style fresh cheeses, such as queso fresco, have relatively low salt content, high water activity, and near neutral pH, which predisposes them to growth of Listeria monocytogenes. Biosafety constraints limit the incorporation of L. monocytogenes into cheeses manufactured via traditional methods in challenge studies, so few have focused on in situ testing of novel antimicrobials in fresh cheeses. We have developed a modular, miniaturized laboratory-scale queso fresco model for testing the incorporation of novel antilisterials. We have demonstrated the assessment of the antilisterials nisin and ferulic acid, alone and in combination, at various levels. Our results support the inhibitory effects of ferulic acid in cheese, against both L. monocytogenes and its common surrogate Listeria innocua, and we provide preliminary evaluation of its consumer acceptability.

Performance of Plasma Biomarkers Combined with Structural MRI to Identify Candidate Participants for Alzheimer's Disease-Modifying Therapy.

BACKGROUND: Recently, two monoclonal antibodies that lower amyloid plaques have shown promising results for the treatment of Mild Cognitive Impairment (MCI) and mild dementia due to Alzheimer's disease (AD). These treatments require the identification of cognitively impaired older adults with biomarker evidence of AD pathology using CSF biomarkers or amyloid-PET. Previous studies showed plasma biomarkers (plasma Aß42/Aß40 and p-tau181) and hippocampal volume from structural MRI correlated with brain amyloid pathology. We hypothesized plasma biomarkers with hippocampal volume would identify patients who are suitable candidates for disease-modifying therapy. OBJECTIVES: To evaluate the performance of plasma AD biomarkers and hippocampal atrophy to detect MCI or AD with amyloid pathology confirmed by amyloid-PET or CSF biomarkers in ADNI. DESIGN: A cross-sectional and longitudinal study. SETTING AND PARTICIPANTS: Data were from the Alzheimer's Disease Neuroimaging Initiative. Participants were aged 55-90 years old with plasma biomarker and structural MRI brain data. MEASUREMENTS: The optimum cut-off point for plasma Aß42/Aß40, p-tau181, and NFL and the performance of combined biomarkers and hippocampal atrophy for detecting cognitive impairment with brain amyloid pathology were evaluated. The association between baseline plasma biomarkers and clinical progression, defined by CDR-Sum of Boxes (CDR-SB) and diagnostic conversion over two years, was evaluated using a Weibull time-to-event analysis. RESULTS: A total of 428 participants were included; 167 had normal cognition, 245 had MCI, and 16 had mild AD. Among MCI and AD, 140 participants had elevated amyloid levels by PET or CSF. Plasma Aß42/Aß40 provided the best accuracy (sensitivity 79%, specificity 66%, AUC 0.73, 95% CI 0.68-0.77) to detect drug candidate participants at baseline. Combined plasma Aß42/40, p-tau181, and hippocampal atrophy increased the specificity for diagnosis (96%), but had lower sensitivity (34%), and AUC (0.65). Hippocampal atrophy combined with the abnormal plasma p-tau181 or hippocampal atrophy alone showed high sensitivity to detect clinical progression (by CDR-SB worsening) of the drug-candidate participants within the next 2 years (sensitivity 93% and 89%, respectively). CONCLUSION: Plasma biomarkers and structural MRI can help identify patients who are currently eligible for anti-amyloid treatment and are likely to progress clinically, in cases where amyloid-PET or CSF biomarkers are not available.

Examining Demographic Factors, Psychosocial Wellbeing and Cardiovascular Health in Subjective Cognitive Decline in the Brain Health Registry Cohort.

BACKGROUND: Subjective cognitive decline (SCD) is defined as an individual's perception of sustained cognitive decline compared to their normal state while still performing within boundaries for normal functioning. Demographic, psychosocial and medical factors have been linked to age-related cognitive decline, and Alzheimer's dementia (AD). However, their relation to risk for SCD remains unclear. This study aims to identify demographic factors, psychosocial and cardiovascular health associated with SCD within the Brain Health Registry (BHR) online cohort. METHODS: Participants aged 55+ (N=27,596) in the BHR self-reported SCD measured using the Everyday Cognition Scale (ECog) and medical conditions, depressive symptoms, body mass index, quality of sleep, health, family history of AD, years of education, race, ethnicity and gender. Multivariable linear regression was used to examine whether SCD was associated with demographic, psychosocial, and medical conditions. RESULTS: We found that advanced age, depressive symptoms, poorer sleep quality and poorer quality of health were positively associated with more self-reported SCD in all models. No race or ethnicity differences were found in association with SCD. Males who reported alcohol and tobacco use or underweight BMI had higher ECog scores compared with females. CONCLUSION: In addition to well-established risk factors for cognitive decline, such as age, our study consistently and robustly identified a strong association between psychosocial factors and self-reported cognitive decline in an online cohort. These findings provide further evidence that psychosocial health plays a pivotal role in comprehending the risk of SCD and early-stage cognitive ageing. Our findings emphasise the significance of psychosocial factors within the broader context of cardiovascular and demographic risk factors.

Short communication: phenotypic and genetic diversity of wild Lactococcus lactis isolated from traditional Pecorino cheeses of Tuscany.

Wild Lactococcus lactis isolates from traditional Pecorino cheeses in 4 regions of Tuscany were isolated and characterized to evaluate the diversity of autochthonous lactococci. Sixty strains of Lactococcus were clustered by the results of carbohydrate utilization and diagnostic enzyme activity. Twenty-one unique strains were then chosen for characterization of salt and temperature tolerance, as well as acidification and proteolytic activity in milk. Genetic analysis of these strains was performed via 16S ribosomal DNA sequencing and multilocus sequence typing (MLST) to elucidate diversity relative to their location of origin. Phylogenetic analysis showed distinct clustering by region within organism subspecies, and phenotypic properties demonstrated concomitant trends. Multilocus sequence typing thus allowed for the regional distinction of isolates separate from those of previous works, supporting the concept that distinctive regional qualities of cheeses are strongly influenced by microbial ecology.

Head-shape polymorphism in Japanese eels Anguilla japonica in relation to differences of somatic growth in freshwater and brackish habitats.

The age, total length (L(T)), head shape and skull shape were investigated for 379 Japanese eels Anguilla japonica sampled in freshwater and brackish areas of the Kojima Bay-Asahi River system, Okayama, Japan, to learn about the differentiation process of head-shape polymorphism. The relative mouth width (ratio of mouth width to L(T)) of A. japonica > 400 mm L(T) collected in fresh water was significantly greater than that of fish collected in brackish water. Growth rates of mouth width and the distance from the snout to the midpoint of the eyes (the ratio of width and distance to age, respectively) were not significantly different between freshwater and brackish-water samples, whereas the somatic growth rate (the ratio of L(T) to age) of freshwater samples was significantly lower than that of brackish-water eel samples. These results suggest that the factors affecting head and somatic growth of A. japonica are not identical. According to these results and feeding patterns in each habitat reported by another study, it is suggested that somatic growth appears to play a significant role in the differentiation process of the head-shape polymorphism in A. japonica, with the slow-growing fish in fresh water becoming broad-headed and the fast-growing fish in brackish water becoming narrow-headed.

Effects of trawling on the diets of common demersal fish by-catch of a tropical prawn trawl fishery.

The ecological effect of prawn trawling on the benthos of the Gulf of Carpentaria, northern Australia, was investigated by examining stomach contents of common demersal fishes incidentally caught as by-catch in the fishery. Fishes were collected from high and low fishing intensity sites in three regions based on vessel monitoring system data. The diets of eight species of benthic fish predators were compared between regions and fishing intensities. A regional effect on diet was evident for seven species. Only one generalist species had no significant difference in diet among the three regions. For the comparisons within each region, five predator species had significantly different diet between high and low fishing intensities in at least one region. Across the three regions, high fishing intensity sites had predators that consumed a greater biomass of crustaceans, molluscs and echinoderms. At low fishing intensity sites, predators had diets comprising a greater biomass of cnidarians and teleosts, and a different assemblage of molluscs, crustaceans and fishes. These changes in diet suggest that there may have been a shift in the structure of the benthic community following intensive fishing. Analysis of predator diets is a useful tool to help identify changes in the benthic community composition after exposure to fishing. This study also provided valuable diet information on a range of abundant generalist benthic predators to improve the ecosystem modelling tools needed to support ecosystem-based fisheries management.

Characterization of a Panela cheese with added probiotics and fava bean starch.

Of 20 Lactobacillus and 8 Bifidobacterium species examined, only Bifidobacterium breve ATCC 15700 was able to ferment starch from fava beans. Bifidobacterium breve ATCC 15700 and Lactobacillus rhamnosus GG ATCC 53103 were selected as probiotics for use in fresh-style Panela cheese. Two types of fresh cheese (with and without 3% fava bean starch) were manufactured with 3 combinations of probiotics: L. rhamnosus GG only, B. breve only, or both L. rhamnosus GG and B. breve. During 4 wk of storage at 4°C, the addition of fava bean starch to the cheese was not found to cause significant differences in the viability of either probiotic strain. However, the microstructure and texture of Panela cheese were altered, resulting in a much softer product. A sensory panel showed that the presence of added fava bean starch in Panela cheese was less desirable to consumers, whereas probiotic supplementation had no effect on perceived taste or appearance. Panela cheese could be a suitable food for inclusion of probiotic bacteria.

Commercial kefir products assessed for label accuracy of microbial composition and density.

Kefirs are fermented beverages containing yeast and bacteria produced by the fermentation of water or milk with kefir grains. Because microorganism density may influence a product's health benefits, label accuracy regarding viable bacterial density and taxonomy of fermented foods is important. In this study, the microbiota of 5 commercial kefir products were measured quantitatively using standard plating techniques and characterized using high-resolution, long-read 16S rRNA gene amplicon sequencing. To enumerate viable lactic acid bacteria, 2 lots of each product were plated on de Man, Rogosa and Sharpe agar upon opening and following 14 d and incubated under anaerobic and aerobic conditions. Results revealed that 66% of products with a guaranteed count of colony-forming units per gram overstated microorganism density by at least 1 log, with only product E exceeding 1 × 109 cfu/g. Sequencing results demonstrated moderate product label accuracy in regard to taxonomy, yet several products contained bacterial species above the minimum detectable threshold (0.001% relative abundance) that were not included on the labels (e.g., Streptococcus salivarius, Lactobacillus paracasei). Our results demonstrate a moderate level of labeling accuracy for commercial kefir products intended for human consumption. Regulatory agencies and consumers must continue to scrutinize these products and demand a higher level of accuracy and quality.

CCR2 regulates monocyte recruitment as well as CD4 T1 allorecognition after lung transplantation.

Graft rejection remains a formidable problem contributing to poor outcomes after lung transplantation. Blocking chemokine pathways have yielded promising results in some organ transplant systems. Previous clinical studies have demonstrated upregulation of CCR2 ligands following lung transplantation. Moreover, lung injury is attenuated in CCR2-deficient mice in several inflammatory models. In this study, we examined the role of CCR2 in monocyte recruitment and alloimmune responses in a mouse model of vascularized orthotopic lung transplantation. The CCR2 ligand MCP-1 is upregulated in serum and allografts following lung transplantation. CCR2 is critical for the mobilization of monocytes from the bone marrow into the bloodstream and for the accumulation of CD11c(+) cells within lung allografts. A portion of graft-infiltrating recipient CD11c(+) cells expresses both recipient and donor MHC molecules. Two-photon imaging demonstrates that recipient CD11c(+) cells are associated with recipient T cells within the graft. While recipient CCR2 deficiency does not prevent acute lung rejection and is associated with increased graft infiltration by T cells, it significantly reduces CD4(+) T(h)1 indirect and direct allorecognition. Thus, CCR2 may be a potential target to attenuate alloimmune responses after lung transplantation.

Sensory and microbiological quality of yogurt drinks with prebiotics and probiotics.

The popularity of dairy products fortified with prebiotics and probiotics continues to increase as consumers desire flavorful foods that will fulfill their health needs. Our objectives were to assess the sensory profile of drinkable yogurts made with prebiotics and probiotics and to determine the viability of the probiotics in the yogurt drink over the duration of storage. Thirteen trained descriptive panelists evaluated 10 yogurt drinks on a 16-point category scale. Three selected prebiotics, soluble corn fiber, polydextrose, and chicory inulin, were each present individually at an amount to claim an excellent source of fiber (5 g of fiber/serving) or a good source of fiber (2.5 g of fiber/serving) in 6 different yogurt drinks. Three additional yogurt drinks contained 5 g of each of the separate prebiotics along with a mixture of the selected probiotics (Bifidobacterium lactis Bb-12 and Lactobacillus acidophilus LA-5). A control sample with no prebiotics or probiotics was also included in the experimental design. Data were analyzed by ANOVA, Fisher's least significant difference, and principal component analysis. Survival of the probiotics in the yogurt drinks during a 30-d refrigerated storage period was also analyzed. Results showed that clover honey aroma, buttermilk aroma, butter aroma, sweetness, sourness, chalky mouthfeel, and viscosity were identified as significant attributes in the yogurt drinks. Total variance explained by the principal component analysis biplot of factors 1 and 2 was 65%, which showed yogurt drinks with soluble corn fiber and inulin varying by the sweet versus sour attributes and yogurt drinks with polydextrose varying by the mouthfeel attributes. The viability study determined a 2- to 3-log decrease in the survival of probiotics in all of the yogurt treatments during a 30-d refrigerated storage period. Based on the results of the current study, only the polydextrose treatment would be an acceptable vehicle to deliver the probiotic health effects at the end of the 30-d storage period.

Morphological and meristic evaluation of the population structure of Anguilla marmorata across its range.

The population structure of the giant mottled eel Anguilla marmorata was evaluated using statistical analysis of 21 morphological characters among 13 representative localities across the Indo-Pacific region and as far north as Japan. There were no clear differences in 15 proportional and six vertebral characters using principal component analysis. The total number of vertebrae (N(V)) of A. marmorata at these localities had the widest variation among the morphological and meristic characters examined. A statistical analysis of the N(V) of 1238 specimens from 14 localities that included previously published data found significant differences among Micronesia, French Polynesia and other localities, and between localities in the North Pacific and South Pacific regions. Few differences were detected between specimens from the Indian Ocean and the North Pacific or South Pacific regions. The differences in N(V) among some regions and the population genetic studies of this species indicate that there are at least four populations of A. marmorata (North Pacific, Micronesia, Indian Ocean and South Pacific), which appear to include metapopulation structures in the Indian Ocean and South Pacific. This population structure is consistent with the ocean current patterns in each region and the evolution of migration loops of each spawning population.

Depth distribution and biological characteristics of the European eel Anguilla anguilla in Lough Ennell, Ireland.

Using a longline survey, a total of 196 European eels Anguilla anguilla were collected at different depths in Lough Ennell (maximum depth 30 m), central Ireland. The catch per unit of effort of A. anguilla that were caught from 1 to 25 m depths was lowest at 0.5-5.0 m and greatest at the deepest depth range (22.5-25.0 m). Sub-samples of A. anguilla from depths of <15 m showed little or no difference in size, sex ratio, age, growth rate, condition factor, length-mass relationship, gonado-somatic index, fin index or eye index with fish from depths of >15 m. All fish examined were female yellow-phase A. anguilla that had ages from 7 to 20 years (mean +/-s.d. = 10.3 +/- 2.9 years), with growth rates from 24.0-60.8 mm year(-1) (mean +/-s.d. = 40.7 +/- 8.5 mm year(-1)). Variations in the growth rates were greater in the shallow group than that of the deep group. This study suggested that deeper regions are important feeding habitats for A. anguilla and that fish in this lake were growing moderately fast compared to similar habitats and areas in the species' range.

Sympatric spawning of Anguilla marmorata and Anguilla japonica in the western North Pacific Ocean.

Extensive collections were made of the larvae of the temperate Japanese eel Anguilla japonica and the tropical giant mottled eel Anguilla marmorata in an overlapping area of the North Equatorial Current region of the western North Pacific Ocean. Collections of 189 A. marmorata and > 2500 A. japonica larvae during nine surveys from 1991 to 2007 showed that these two anguillid eels have similar spawning areas just west of the southern West Mariana Ridge. In July to August 2006 and August 2007, morphologically and genetically identified A. marmorata preleptocephali were mainly collected between 14.5-15 degrees N and 142-142.5 degrees E, where A. japonica preleptocephali were also caught in some of the same net tows. Fewer A. marmorata preleptocephali, however, were collected (n = 31) compared to those of A. japonica (n = c. 165), and fewer small larvae of A. marmorata were collected per tow than A. japonica (n = 1-10 and 1-294, respectively), suggesting relatively smaller spawning aggregations of A. marmorata. The distribution of preleptocephali and small larvae was wider in longitude in A. marmorata (131- 143 degrees E) than in A. japonica (137-143 degrees E), while the latitudinal range was almost the same (12-17 degrees N). Although spawning by these two species overlaps both spatially and temporally, the tropical eels of the North Pacific population of A. marmorata probably have a much longer spawning season with fewer spawners, at least in summer, and recruit to a much wider latitudinal range of growth habitats.

Clinical presentation of delayed hemolytic transfusion reactions and hyperhemolysis in sickle cell disease.

Red blood cell (RBC) transfusion therapy is a key component in the comprehensive management of patients with sickle cell disease (SCD). Consequently, most adult SCD patients will receive at least one, and many will receive more than a hundred RBC transfusions in their lifetime. SCD patients develop RBC alloantibodies much more frequently than non-SCD transfused patients, which often make the selection of compatible RBCs extremely difficult, in addition to placing patients at significantly higher risk of suffering from delayed hemolytic transfusion reactions (DHTRs). Similar to alloimunization, DHTRs are much more common in patients with SCD compared to other heavily transfused populations, and are particularly consequential due to their propensity to cause hyperhemolysis, a life-threatening phenomenon in which both transfused RBCs in addition to the patient's own sickle-erythrocytes are destroyed. In this review, we highlight the incidence and pathophysiology of DHTRs; illustrate common presentations, appropriate evaluations and outcomes of DHTRs in patients with SCD; and discuss strategies for preventing or reducing the likelihood of DHTRs from occurring.