Functional genomics provides insights into the role of Propionibacterium freudenreichii ssp shermanii JS in cheese ripening

Propionibacterium freudenreichii is a commercially important bacterium that is essential for the development of the characteristic eyes and flavor of Swiss-type cheeses. These bacteria grow actively and produce large quantities of flavor compounds during cheese ripening at warm temperatures but also appear to contribute to the aroma development during the subsequent cold storage of cheese. Here, we advance our understanding of the role of P. freudenreichii in cheese ripening by presenting the 2.68-Mbp annotated genome sequence of P. freudenreichii ssp. shermanii JS and determining its global transcriptional profiles during industrial cheese-making using transcriptome sequencing. The annotation of the genome identified a total of 2377 protein-coding genes and revealed the presence of enzymes and pathways for formation of several flavor compounds. Based on transcriptome profiling, the expression of 348 protein-coding genes was altered between the warm and cold room ripening of cheese. Several propionate, acetate, and diacetyl/acetoin production related genes had higher expression levels in the warm room, whereas a general slowing down of the metabolism and an activation of mobile genetic elements was seen in the cold room. A few ripening-related and aminoacid catabolism involved genes were induced or remained active in cold room, indicating that strain JS contributes to the aroma development also during cold room ripening. In addition, we performed a comparative genomic analysis of strain JS and 29 other Propionibacterium strains of 10 different species, including an isolate of both P. freudenreichii subspecies freudenreichii and shermanii. Ortholog grouping of the predicted protein sequences revealed that close to 86% of the ortholog groups of strain JS, including a variety of ripening-related ortholog groups, were conserved across the P. freudenreichii isolates. Taken together, this study contributes to the understanding of the genomic basis of P. freudenreichii and sheds light on its activities during cheese ripening. (C) 2016 Elsevier B.V. All rights reserved.Peer reviewe

Long-term outcome after treatment of pulmonary atresia with ventricular septal defect : nationwide study of 109 patients born in 1970-2007

OBJECTIVES: Treatment of pulmonary atresia with ventricular septal defect (PA + VSD) has evolved during recent decades, but it still remains challenging. This study evaluated 41-year experience of outcome, survival and treatment of PA + VSD patients. METHODS: Patient records and angiograms of 109 patients with PA + VSD born in Finland between 1970 and 2007, and treated at the Children's Hospital, Helsinki University Central Hospital, were retrospectively analysed in this nationwide study. RESULTS: Of the 109 patients, 66 (61%) had simple PA + VSD without major aortopulmonary collateral arteries (MAPCAs). Although we observed no difference in overall survival between those with or without MAPCAs, the patients without MAPCAs had better probability to achieve repair (64 vs 28%, P <0.0003). Only 3 patients were treated by compassionate care. Overall survival was affected by the size of true central pulmonary arteries on the first angiogram (P = 0.001) and whether repair was achieved (P <0.0001). After successful repair, the survival rate was 93% at 1 year, 91% from the second year, and functional capacity as assessed by New York Heart Association (NYHA) I-II remained in 85% of patients alive at the end of follow-up. Palliated patients at 1, 5, 10 and 20 years of age had Kaplan-Meier estimated survival rates of 55, 42, 34 and 20%, respectively. Patients who underwent repair attempts but were left palliated with right ventricle (RV)-pulmonary artery connection and septal fenestration had better survival than the rest of the palliated patients (P = 0.001). Further, the McGoon index improved after implementation of a systemic-pulmonary artery shunt in the overall PA + VSD population (P <0.0001). CONCLUSIONS: These findings show that achievement of repair and initial size of true central pulmonary arteries affect survival of patients with PA + VSD. Although the overall survival of patients with MAPCAs showed no difference compared with simple PA + VSD patients, they had a higher risk of remaining palliated. However, palliative surgery may have a role in treatment of PA + VSD because the size of pulmonary arteries increased after placement of systemic-pulmonary artery shunt. In addition, subtotal repair by a RV-pulmonary artery connection and septal fenestration improved survival over extracardiac palliation.Peer reviewe

Ab initio study of the surface properties of austenitic stainless steel alloys

Using ab initio calculations we investigated the surface energies of paramagnetic Fe1-c-nCrcNin random alloys within the concentration range of 0.12 &lt;= c &lt;= 032 and 0.04 &lt;= n &lt;= 0.32. These alloys crystallize mainly in the face centred cubic (fcc) structure and constitute the main building blocks of austenitic stainless steels. It is shown that all alloys have the lowest surface energies along the most close packed crystal orientation, namely the fcc (111) surfaces. The amount of Ni seems to have little effect on the surface energy, while almost all composition-driven change may be attributed to the changes in the Cr content. Within the studied compositional range, the change of the surface energy with the composition is of the order of 10%. Trends of the surface energy can be related to the magnetic structure of surfaces. Using the total energy as a function of the concentration, we determine the effective chemical potentials in bulk and at the surface, which can be used to estimate the surface segregation energies. (C) 2012 Elsevier B.V. All rights reserved

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

Loss of p53 results in protracted electrographic seizures and development of an aggravated epileptic phenotype following status epilepticus

The p53 tumor suppressor is a multifunctional protein, which regulates cell cycle, differentiation, DNA repair and apoptosis. Experimental seizures up-regulate p53 in the brain, and acute seizure-induced neuronal death can be reduced by genetic deletion or pharmacologic inhibition of p53. However, few long-term functional consequences of p53 deficiency have been explored. Here, we investigated the development of epilepsy triggered by status epilepticus in wild-type and p53-deficient mice. Analysis of electroencephalogram (EEG) recordings during status epilepticus induced by intra-amygdala kainic acid (KA) showed that seizures lasted significantly longer in p53-deficient mice compared with wild-type animals. Nevertheless, neuronal death in the hippocampal CA3 subfield and the neocortex was significantly reduced at 72 h in p53-deficient mice. Long-term continuous EEG telemetry recordings after status epilepticus determined that the sum duration of spontaneous seizures was significantly longer in p53-deficient compared with wild-type mice. Hippocampal damage and neuropeptide Y distribution at the end of chronic recordings was found to be similar between p53-deficient and wild-type mice. The present study identifies protracted KA-induced electrographic status as a novel outcome of p53 deficiency and shows that the absence of p53 leads to an exacerbated epileptic phenotype. Accordingly, targeting p53 to protect against status epilepticus or related neurologic insults may be offset by deleterious consequences of reduced p53 function during epileptogenesis or in chronic epilepsy

Lumbar segmental mobility disorders: comparison of two methods of defining abnormal displacement kinematics in a cohort of patients with non-specific mechanical low back pain

BACKGROUND: Lumbar segmental rigidity (LSR) and lumbar segmental instability (LSI) are believed to be associated with low back pain (LBP), and identification of these disorders is believed to be useful for directing intervention choices. Previous studies have focussed on lumbar segmental rotation and translation, but have used widely varying methodologies. Cut-off points for the diagnosis of LSR & LSI are largely arbitrary. Prevalence of these lumbar segmental mobility disorders (LSMDs) in a non-surgical, primary care LBP population has not been established. METHODS: A cohort of 138 consecutive patients with recurrent or chronic low back pain (RCLBP) were recruited in this prospective, pragmatic, multi-centre study. Consenting patients completed pain and disability rating instruments, and were referred for flexion-extension radiographs. Sagittal angular rotation and sagittal translation of each lumbar spinal motion segment was measured from the radiographs, and compared to a reference range derived from a study of 30 asymptomatic volunteers. In order to define reference intervals for normal motion, and define LSR and LSI, we approached the kinematic data using two different models. The first model used a conventional Gaussian definition, with motion beyond two standard deviations (2sd) from the reference mean at each segment considered diagnostic of rotational LSMD and translational LSMD. The second model used a novel normalised within-subjects approach, based on mean normalised contribution-to-total-lumbar-motion. An LSMD was then defined as present in any segment that contributed motion beyond 2sd from the reference mean contribution-to-normalised-total-lumbar-motion. We described reference intervals for normal segmental mobility, prevalence of LSMDs under each model, and the association of LSMDs with pain and disability. RESULTS: With the exception of the conventional Gaussian definition of rotational LSI, LSMDs were found in statistically significant prevalences in patients with RCLBP. Prevalences at both the segmental and patient level were generally higher using the normalised within-subjects model (2.8 to 16.8% of segments; 23.3 to 35.5% of individuals) compared to the conventional Gaussian model (0 to 15.8%; 4.7 to 19.6%). LSMDs are associated with presence of LBP, however LSMDs do not appear to be strongly associated with higher levels of pain or disability compared to other forms of non-specific LBP. CONCLUSION: LSMDs are a valid means of defining sub-groups within non-specific LBP, in a conservative care population of patients with RCLBP. Prevalence was higher using the normalised within-subjects contribution-to-total-lumbar-motion approach

Coronary artery bypass surgery in high-risk patients

BACKGROUND: In high-risk coronary artery bypass patients; off-pump versus on-pump surgical strategies still remain a matter of debate, regarding which method results in a lower incidence of perioperative mortality and morbidity. We describe our experience in the treatment of high-risk coronary artery patients and compare patients assigned to on-pump and off-pump surgery. METHODS: From March 2002 to July 2004, 86 patients with EuroSCOREs > 5 underwent myocardial revascularization with or without cardiopulmonary bypass. Patients were assigned to off-pump surgery (40) or on-pump surgery (46) based on coronary anatomy coupled with the likelihood of achieving complete revascularization. RESULTS: Those patients undergoing off-pump surgery had significantly poorer left ventricular function than those undergoing on-pump surgery (28.6 ± 5.8% vs. 40.5 ± 7.4%, respectively, p < 0.05) and also had higher Euroscore values (7.26 ± 1.4 vs. 12.1 ± 1.8, respectively, p < 0.05). Differences between the two groups were nonsignificant with regard to number of grafts per patient, mean duration of surgery, anesthesia and operating room time, length of stay intensive care unit (ICU) and rate of postoperative atrial fibrillation CONCLUSION: Utilization of off-pump coronary artery bypass graft (CABG) does not confer significant clinical advantages in all high-risk patients. This review suggest that off-pump coronary revascularization may represent an alternative approach for treatment of patients with Euroscore ≥ 10 and left ventricular function ≤ 30%

Schistosomiasis among Recreational Users of Upper Nile River, Uganda, 2007

After recreational exposure to river water in Uganda, 12 (17%) of 69 persons had evidence of schistosome infection. Eighteen percent self-medicated with praziquantel prophylaxis immediately after exposure, which was not appropriate. Travelers to schistosomiasis-endemic areas should consult a travel medicine physician

Chagasic Thymic Atrophy Does Not Affect Negative Selection but Results in the Export of Activated CD4+CD8+ T Cells in Severe Forms of Human Disease

Extrathymic CD4+CD8+ double-positive (DP) T cells are increased in some pathophysiological conditions, including infectious diseases. In the murine model of Chagas disease, it has been shown that the protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironment and the lymphoid compartment. In the acute phase, this results in a severe atrophy of the organ and early release of DP cells into the periphery. To date, the effect of the changes promoted by the parasite infection on thymic central tolerance has remained elusive. Herein we show that the intrathymic key elements that are necessary to promote the negative selection of thymocytes undergoing maturation during the thymopoiesis remains functional during the acute chagasic thymic atrophy. Intrathymic expression of the autoimmune regulator factor (Aire) and tissue-restricted antigen (TRA) genes is normal. In addition, the expression of the proapoptotic Bim protein in thymocytes was not changed, revealing that the parasite infection-induced thymus atrophy has no effect on these marker genes necessary to promote clonal deletion of T cells. In a chicken egg ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic system, the administration of OVA peptide into infected mice with thymic atrophy promoted OVA-specific thymocyte apoptosis, further indicating normal negative selection process during the infection. Yet, although the intrathymic checkpoints necessary for thymic negative selection are present in the acute phase of Chagas disease, we found that the DP cells released into the periphery acquire an activated phenotype similar to what is described for activated effector or memory single-positive T cells. Most interestingly, we also demonstrate that increased percentages of peripheral blood subset of DP cells exhibiting an activated HLA-DR+ phenotype are associated with severe cardiac forms of human chronic Chagas disease. These cells may contribute to the immunopathological events seen in the Chagas disease