Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus.
Respiratory syncytial virus (RSV) is one of the main pathogens associated with lower respiratory tract infections in infants and young children worldwide. Exosomes secreted by antigen presenting cells (APCs) can elicit immune responses by carrying major histocompatibility complex (MHC) class I molecules complexed with antigenic peptides and other co-stimulating factors. Therefore, we developed novel immunomagnetic nanographene particles to sequentially isolate, surface engineer, and release intact dendritic cell (DC) exosomes for use as a potential vaccine platform against RSV. The H-2Db-restricted, immunodominant peptides from RSV (M187-195 and NS161-75) were introduced to MHC-I on DC-derived exosomes to express peptide/MHC-I (pMHC-I) complexes. A mouse model of RSV infection was used to define the immunogenicity of surface engineered exosomes for activating virus-specific immune responses. Ex vivo assays demonstrated that engineered exosomes carrying RSV-specific peptides can elicit interferon-gamma (IFN-γ) production by virus-specific CD8+ T cells isolated from RSV-infected C57BL/6 mice. In vivo assays demonstrated that subcutaneous administration of both M187-195 and NS161-75 engineered exosomes to mice, with or without additional adjuvant, appeared safe and well tolerated, however, did not prime antigen-specific CD8+ T cell responses. Surface engineered exosomes are immunogenic and promising for further development as a vaccine platform.


Sonographic prenatal diagnosis of central nervous system abnormalities.
Over the past 20 years, the spectrum of neonatal neurological malformations has changed due to the diffusion of ultrasound, performed either routinely or as required by maternal alpha-fetoprotein screening or history. We review and illustrate the potential of ultrasound for the prenatal diagnosis of abnormalities in size or shape of the skull (macrocephaly, microcephaly, craniostenosis), neural tube defects, ventriculomegaly, hydrocephalus, posterior fossa defects (abnormalities in the size of the cisterna magna, cerebellar abnormalities), midline abnormalities (holoprosencephaly, abnormalities of the corpus callosum), ischemic lesions and hemorrhage, tumours, and focalized hyperechogenic images. The limits of fetal ultrasound screening and of the various diagnostic strategies implemented when a fetal brain abnormality is suspected are discussed. Overall, gross lethal abnormalities such as anencephaly or major hydrocephaly are accessible to prenatal sonographic screening, and nearly always result in termination of the pregnancy. However, hydrocephaly may progress late in gestation and remain undiscovered unless a third trimester ultrasound is performed. A majority of cases with myelomeningocele are diagnosed prenatally, resulting either in termination of the pregnancy or in neonatal management. A growing number of more subtle abnormalities, including midline or posterior fossa abnormalities can be spotted by fetal ultrasound, but their postnatal outcome cannot always be predicted accurately, despite the use of fetal magnetic resonance imaging. In such cases, a trans-disciplinary approach involving perinatologists, pediatric radiologists, neuropathologists, neurosurgeons or neurologists familiar with neonates is crucial to counseling the parents. Some brain abnormalities are still extremely difficult or even impossible to diagnose in utero despite advances in sonographic imaging. This is due to the fact that severe neurological impairment may result from conditions that do not affect substantially affect the morphology of the brain, and that major structural abnormalities may develop late in gestation, and thus remain undetected at second trimester ultrasound. Ultrasound screening identifies a growing number of central nervous system abnormalities, resulting in substantial changes in the neonatal presentation of neurological congenital abnormalities.


Limosina brachystoma can be reared even when the food and substratum (dry leaves of Urtica or almost any other plant) are moistened with 15‰ NaCl p.a. or with 15‰ NaCl plus KCl. Orchestia lives about three weeks if kept on a substratum moistened with a solution of 15‰ NaCl (Food: Fucus).H2SO4, on the other hand, is fatal especially, for Orchestia.Burning oil gives off pollutants into the surrounding water. These pollutants are fatal for all the animals studied even at very low concentrations. But in air (not in water) these pollutants disappear within one week and the substratum may be colonized again.Crude oil which has floated in the sea for a long time is not any longer poisonous to the animals studied. It does not hinder rapid propagation of all species Larvae of the flies and - to a lesser extent - of the amphipodes rummage in their substratum and disperse a big piece of old crude oil into fine parts throughout the petri dish.


Risk factors for problem behavior in adolescents of parents with a chronic medical condition.
A wide array of risk factors for problem behavior in adolescents with chronically ill parents emerges from the literature. This study aims to identify those factors with the highest impact on internalizing problem behavior (anxious, depressed and withdrawn behavior, and somatic complaints) and externalizing problem behavior (aggressive and rule-breaking behavior) as measured by the Youth Self-Report (YSR). The YSR was filled in by 160 adolescents (mean age = 15.1 years) from 100 families (102 chronically ill parents and 83 healthy spouses). Linear mixed model analyses were used, enabling separation of variance attributable to individual factors and variance attributable to family membership (i.e., family cluster effect). Predictors were child, parent, illness-related and family characteristics. The results showed that almost half of the variance in internalizing problem scores was explained by family membership, while externalizing problems were mainly explained by individual factors. Roughly 60 % of the variance in internalizing problems was predicted by illness duration, adolescents' feeling of isolation, daily hassles affecting personal life and alienation from the mother. Approximately a third of the variance in externalizing problems was predicted by adolescents' male gender, daily hassles concerning ill parents and alienation from both parents. In conclusion, the variance in adolescent problem behavior is largely accounted for by family membership, children's daily hassles and parent-child attachment. To prevent marginalization of adolescents with a chronically ill parent, it is important to be alert for signs of problem behavior and foster the peer and family support system.


Effect of isovolemic hemodilution in central retinal vein occlusion.
Hemorheologic abnormalities have recently been shown to play a role in the pathogenesis of retinal vein occlusion (RVO), and several studies have demonstrated the efficacy of isovolemic hemodilution in these eyes. This study was designed to investigate further the effects of hemodilution, with regard to the duration of symptoms before the treatment. In a prospective study, 142 eyes with central or hemicentral RVO were treated by isovolemic hemodilution. The target hematocrit value was 35%. Mean duration of follow-up was 10 months. A subgroup of 50 patients treated within 2 weeks of the onset of symptoms was compared first with patients treated later by hemodilution, and then retrospectively with controls with central RVO and without hemodilution. Hemodilution therapy resulted in a decrease in hematocrit level from 42% to 32% on average, with no major side effect. After treatment, a significant decrease was observed in hemorheologic parameters (fibrinogen, erythrocyte aggregation), except in plasma viscosity. Retinal circulation times were significantly shortened. Visual acuity (VA) improvement immediately after treatment (in 43% of eyes) was correlated with better final visual outcome (P<0.05). At the end of follow-up, VA was better in patients treated within the first 2 weeks than in those treated later and in controls (41% had VA of 20/40 or more in the early-treatment group versus 23% in the late-treatment group, P<0.01). Final retinal ischemia was also greater in the late-treatment group and in controls. Hemodilution in 12 patients with long-standing RVO and macular edema was ineffective. Our study is consistent with previous investigations that confirmed the efficacy of isovolemic hemodilution in RVO on hemorheologic parameters, retinal circulation times and final VA. It also underlined strongly the benefit of early treatment within the first 2 weeks of the RVO. Further studies are required to confirm these results.


Microbial Signatures and Innate Immune Gene Expression in Lamina Propria Phagocytes of Inflammatory Bowel Disease Patients.
The interaction between intestinal microbiota and the immune system plays a vital role in inflammatory bowel disease (IBD). Although numerous deep-sequencing studies have suggested dysbiosis in IBD, identifying specific bacteria from the stool or mucosa that are responsible for disease susceptibility or severity has remained a challenge. Lamina propria phagocytes ideally are localized to interact with bacteria that are in close proximity to, or have invaded, the tissue. Thus, we examined the microbial populations associated with the lamina propria phagocytes in 20 Crohn's disease and 12 ulcerative colitis patients. Specifically, we aimed to address whether the phagocyte-associated microbiota differed from the mucosa-associated microbiota and whether this varied based on IBD type or the state of inflammation. 16S ribosomal RNA gene sequencing and innate immune gene expression profiling was done on CD11b+ lamina propria phagocytes isolated from the biopsies obtained from IBD patients. Phagocyte-associated microbiota was enriched in bacterial species belonging to phylum Proteobacteria, whereas species belonging to phylum Bacteroidetes were enriched in the mucosal microbiota of IBD patients. Disease type was the most influential factor in driving differences in the microbiota of both the mucosa and the lamina propria phagocytes, irrespective of inflammation state o`r anatomic location. Crohn's disease and ulcerative colitis specimens showed similar patterns of increased inflammatory gene expression in phagocytes isolated from inflamed areas compared with those isolated from uninflamed regions. This pilot study shows the feasibility of using lamina propria phagocytes to characterize the microbiota in IBD patients. The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations and clinically relevant gene expression signatures in IBD patients.


Expression of human telomerase reverse transcriptase in bone marrow CD34+ cells from patients with beta-thalassemia major.
Normal stem cells usually express a low level of telomerase activity that serves to stabilize the chromosomes during cell division and helps prevent cell senescence. Human telomerase reverse transcriptase (hTERT) is a rate-limiting enzyme that dictates the activity of human telomerase and thus decides the life span of cells. The expression of hTERT and its roles in beta-thalassemia major are unclear, however. hTERT mRNA expression in bone marrow (BM) CD34+ cells from 25 children with beta-thalassemia major and 15 control subjects was investigated using real-time reverse transcription polymerase chain reaction (RT-PCR) analysis. The serum erythropoietin (sEPO) and hemoglobin (Hb) levels in peripheral blood were also determined. The relationship between hTERT and sEPO as well as Hb was then examined. It was found that hTERT mRNA expression was significantly up regulated in BM CD34+ cells from patients with beta-thalassemia major. Furthermore, a significantly positive correlation was found between hTERT mRNA and sEPO (r = 0.771, p < 0.001). A significantly inverse correlation, however, was found between hTERT mRNA and Hb concentration (r = -0.929, p < 0.001). Our findings suggest that severe anemia with low Hb concentration might up regulate hTERT expression of BM CD34+ cells and sEPO levels in patients with beta-thalassemia major.


Synthesis and cytotoxic evaluation of 1-carboxamide and 1-amino side chain substituted β-carbolines.
The condensation of alkylenediamine with ethyl β-carboline-1-carboxylate and 1-bromo-β-carboline gave β-carboline-1-carboxamides and 1-amino-β-carbolines, respectively. Some of these β-carbolines were active against a panel of human tumor cell lines, and 1-amino derivatives were more potent than their 1-carboxamide congeners. In particular, among the 1-amino-β-carbolines, the N(9)-arylated alkyl substituted β-carbolines exhibited the most interesting cytotoxic activities with IC(50) value of lower than 20 μM. The preliminary structure-activity relationships (SARs) analysis suggested that (1) 1-amino substituents were the advisable pharmacophoric group for enhanced cytotoxic activities; (2) the introduction of appropriate arylated alkyl groups into position-9 of β-carboline facilitated their cytotoxic potencies.


Cryptococcus albidus keratitis after corneal transplantation.
To report suspected donor-to-host transmission of Cryptococcus albidus after penetrating keratoplasty. Review of the literature and a case report of a 69-year-old woman who underwent penetrating keratoplasty for Fuchs corneal dystrophy and developed persistent corneal infiltrates 7 months postoperatively are presented. Cryptococcus albidus was cultured from the original donor tissue at the time of the repeat keratoplasty. This case demonstrates an unusual case of cryptococcal keratitis after keratoplasty suspected to be a donor-to-host transmission.


Localization of the pool of G4 acetylcholinesterase characterizing fast muscles and its alteration in murine muscular dystrophy.
The distributions of acetylcholinesterase and its molecular forms within muscles of normal and dystrophic 129/ReJ mice were established by a concomitant cytochemical and biochemical study performed on 1-mm serial sections of three predominantly fast muscles, i.e., anterior tibialis, extensor digitorum longus, and sternomastoid, as well as the slow-twitch soleus. This comparative study showed the following main findings. 1) In every muscle of both normal and dystrophic mice a) the three asymmetric forms were confined to the motor zone where they systematically codistributed with the endplates, and b) all globular forms, including G4, were concentrated at the motor zone from which they extended over the entire muscle length along a concentration gradient. 2) In the normal muscles, the perijunctional sarcoplasmic cytochemical reaction exhibited by individual fibers was grouped into a well-defined cojunctional acetylcholinesterase compartment in which the endplates were embedded. The overall intensity of the cojunctional cytochemical reaction was either high or low according to whether the muscle was predominantly fast or slow. 3) This cojunctional acetylcholinesterase compartment varied in close parallelism with G4 and thus appeared as the cytochemical correlate of the G4 molecules concentrated around the endplates. In particular, as the shape of the motor zone progressively increased in complexity along with the intricacy of the muscle fiber organization, from sternomastoid to extensor digitorum longus to anterior tibialis, so did both the relative volume occupied by the cojunctional acetylcholinesterase compartment and the proportion of G4. 4) The motor zone of the normal fast-twitch muscles characteristically differed from that of the soleus by the presence of a G4-rich environment around the endplates, which was cooperatively provided by the surrounding fibers. 5) In dystrophic muscles, this cojunctional G4-rich compartment was lost: the cojunctional cytochemical compartment was no longer discernable, while G4 was reduced to a minimal low level similar to that characteristic of the normal soleus.


Health counseling and health promotion of musculoskeletal disorders.
The steady increase in the number of musculoskeletal disorders has heightened the importance of health promotion accordingly. In Germany, health promotion efforts have become the responsibility of health insurers. Commissioned by the health insurance organization, Hamburg-Münchener Ersatzkasse, we developed and evaluated a new health counseling service for persons with musculoskeletal (rheumatic) complaints. In order to draft the scope and principles of the counseling program, we questioned more than 1000 enrollees per questionnaire. The aim of the survey was to estimate the actual demand for participation in the health counseling. The results show that the subjective need for health counseling is strongly linked to the kind of physical limitation involved, so that it can be assumed that particularly persons with relevant complaints and musculoskeletal disorders will participate in the program. To evaluate the counseling sessions, a range of measurements was developed. The aim was to obtain a comprehensive and precise record of the problems and complaints of those taking part in the program. The evaluation shows that the new service is used mainly by persons who have suffered limitations to their health for years due to musculoskeletal disorders. Especially middle-aged persons use the counseling service, with women showing the most interest. When participants were asked after counseling which health support measures they had taken or were planning, their answers indicated that in most cases the recommendations of the counselor were being put into practice. We conclude that health counseling can be considered a meaningful option for health promotion.


Himalayan alpine ecohydrology: An urgent scientific concern in a changing climate.
Climate change is projected to have important impacts on snow and vegetation distribution in global mountains. Despite this, the coupling of ecological shifts and hydrological processes within alpine zones has not attracted significant scientific attention. As the largest and one of the most climatically sensitive mountain systems, we argue that Himalayan alpine ecohydrological processes require urgent scientific attention because up to 1.6 billion people rely on water supplies from the mountains. We review studies from global mountain systems to highlight the importance of considering ecohydrological impacts within Himalayan alpine zones (4100-6000 m.a.s.l), explaining mechanisms for interactions between snow and dwarf plants. Our findings highlight the paucity of monitoring stations within Himalayan alpine systems. We suggest that it is likely that alpine ecological shifts will impact hydrological processes, but we found that specific mechanisms and functional relationships are missing for Himalayan systems, so the strength and direction of ecohydrological relationships is currently unknown. We advocate for more purposeful and widespread monitoring efforts below glaciers and above the treeline, calling for new experiments to query the role of small plants within the Himalayan alpine hydrological system. We outline the need for community engagement with alpine ecohydrological experiments, and we explain how new snow and vegetation products derived from remote sensing observations have the potential to improve scientific understanding of the interacting effects of warming and ecohydrological factors in this sensitive region.


Proposed signaling role of arachidonic acid in human myometrium.
The objective of this study was to test the hypothesis that, in human myometrial cells (HMC), PGF2 alpha and oxytocin promote the release of arachidonic acid (AA) which, in turn, acts to mobilize intracellular Ca2+. Primary monolayer cultures of HMC were labeled with [3H]arachidonic acid ([3H]AA) to isotopic equilibrium before exposure to PGF2 alpha or oxytocin. Radiolabeled phospholipids were separated on thin layer chromatography and quantitated by scintillation counting. Prostanoids were analyzed by high performance liquid chromatography. Calcium release was quantitated in digitonin-permeabilized myocytes preloaded with 45Ca, in the presence of ATP and ruthenium red. PGF2 alpha (10(-7) M) caused a rapid (peaking at 2 min), and significant (P < 0.01) increase in [3H]AA release that was derived selectively from phosphatidylethanolamine (PE), indicative of phospholipase A2 activation. Oxytocin caused a rapid (30 s) and significant increase in diacylglycerol, concomitant with a drop in phosphoinositides, as well as an increase in [3H]AA and a fall in PE and phosphatidylcholine. Exogenous AA caused a rapid and dose-related efflux of 45Ca2+, which was not inhibited by blockers of AA metabolism, or by heparin that abolished inositol 1,4,5-trisphosphate-induced 45Ca2+ release. It is concluded that PGF2 alpha and oxytocin promote, by different mechanisms, the release of AA, which in turn may amplify their action by enhancing Ca2+ mobilization from the sarcoplasmic reticulum, thereby fulfilling the role of intracellular signaling molecule in human myometrium.


[Evaluating multislice computed tomography for imaging coronary atherosclerosis].
The purpose of this study was the evaluation of multidetector-row computed tomography (MDCT) for the assessment of atherosclerotic coronary artery vessel wall changes. In an ex vivo study, 17 human hearts were scanned with MDCT and results were compared to histopathology. Morphologic imaging criteria of MDCT for various plaque-types were developed. In a following in vivo study, 94 coronary MDCT angiograms (MDCTA) of patients with suspected coronary artery disease (CAD) were reviewed retrospectively, assessing the diagnostic value of the coronary MDCTA, and determining the number and correlations of the various plaques types as described in the ex vivo study. Additionally, volumetry of calcified and noncalcified plaque components was performed. In the ex vivo study, MDCT showed a high sensitivity for calcified and non-calcified plaques. Comparing the results with histopathology, characteristic image criteria could be determined for lipid-rich, fibrous and calcified plaque components. Reviewing the contrastenhanced in-vivo MDCT coronary angiographies, presence of noncalcified plaques was proven in 38% of the patients. In 5 patients with a calcium score of 0, presence of coronary atherosclerosis was proven in the contrastenhanced scan. MDCT is able to differentiate various plaque components in an ex vivo setting as well as invivo. Contrastenhanced MDCT of the coronary arteries allows for the detection of noncalcified plaques. In vivo volumetry of noncalcified plaques is feasible.


Cytoprotective antioxidant activity of serum albumin and autocrine catalase in chronic lymphocytic leukaemia.
Chronic lymphocytic leukaemia (CLL) cells are long lived in vivo but undergo spontaneous apoptosis when cultured in vitro. Intriguingly, CLL cells also appear to have a specific susceptibility to oxidative stress - a potent inducer of apoptosis. Here, we show that serum albumin can function as a cytoprotective antioxidant of potential relevance to circulating CLL cells, and that autocrine catalase - a hydrogen peroxide-inactivating enzyme that may be released extracellularly - can perform a similar role under the crowded conditions that prevail at sites of tissue involvement. Albumin lowered oxidative stress in cultured CLL cells and inhibited spontaneous and reactive oxidant-induced apoptosis. Maximal effects were observed at a concentration of 10 mg/ml - fourfold lower than that in plasma and twofold higher than that in standard culture medium containing 10% fetal calf serum. Oxidative stress and spontaneous apoptosis were also decreased by cell crowding and by conditioned medium (CM) from crowded CLL cells, indicating that these processes were subject to autocrine regulation. CLL cells were found to express catalase and release enzyme activity into the culture medium. Exogenous catalase decreased oxidative stress and spontaneous apoptosis, and the anti-apoptotic effect of CM from crowded CLL cells was abrogated by the specific catalase inhibitor, 3'-amino-1,2,4-triazole. Together, these data strongly implicate autocrine catalase as a cytoprotective antioxidant. Oxidative stress in CLL cells was greatly diminished by ruthenium red - an inhibitor of mitochondrial reactive oxidant production - and by the glutathione (GSH) precursor N-acetylcysteine, suggesting that the GSH peroxidase antioxidant system may be compromised by lack of available substrate. Our findings highlight the importance of endogenous reactive oxidants in regulating CLL-cell apoptosis, and help to explain why CLL cells survive for prolonged periods in vivo despite their vulnerability to oxidative stress and spontaneous apoptosis when cultured in vitro.


Editorial for Special Issue: "Recent Advances in Green Solvents".
Today, environmental conservation is one of the most urgent targets [...].


BVDV infection risk in the course of the voluntary BVDV eradication program in Styria/Austria.
A total of 1362 persistently BVDV-infected animals were identified in 850 herds during the first 3 years of the voluntary BVDV eradication program in Styria/Austria. Within the same period of time, the prevalence of BVDV-infected herds dropped from 7.3% to 2.2% of the 4412 herds covered by the program. The relative BVDV infection risk decreased at least four-fold in herds on common grazing and at least five-fold in herds which purchased cattle during the first 30 months of the BVD control program. Thus, the relative BVDV infection risk was reduced by between five to nine times of the initial risk following the implementation of the 3-year eradication program in all herds participating in the program.


Effect of home-based exercise intervention on fasting insulin and Adipocytokines in colorectal cancer survivors: a randomized controlled trial.
Elevated circulating insulin is associated with increased risk of recurrence and cancer mortality in early-stage colorectal cancer (CRC). We conducted a randomized controlled trial to determine the effect of a 12-week home-based exercise program on fasting insulin, adipocytokines, and physical function in CRC survivors. One hundred and twenty-three stage II-III CRC patients were randomly assigned to either a home-based exercise (n=62) or standard care control group (n=61) for 12weeks. Home-based exercise consisted of aerobic and resistance training, with a goal of obtaining ≥18 metabolic equivalent task (MET)-h/wk. Participants in the exercise group were instructed to participate in >18MET-h/wk. of aerobic and resistance exercise while the participants in the control group were asked to maintain their usual daily activity. The primary outcome was fasting insulin levels. Secondary outcomes were adiponectin, TNF-α levels and 6min walk distance from baseline to post-intervention. After the 12-weeks, moderate-vigorous physical activity participation increased from 9.1±14.7MET-h/wk. to 26.6±21.7MET-h/wk. in the exercise group, with no change in the control group (p<0.01 for group and time interaction). Circulating insulin level decreased by 1μU/ml (6.0±3.9 vs. 5.0±3.5, p=0.009) in the exercise group with no change in the control group (p=0.022 for group and time interaction). A similar trend was observed in TNF-α (p=0.030 for group and time interaction). Six minute walk distance increased by 25.2m in the exercise group with no change in the control group (p=0.061 for group and time interaction). The 12week home-based exercise program increased level of physical activity and decreased circulating insulin levels in CRC survivors.


In vitro lipid metabolism in the rat pancreas. I. Basal lipid metabolism.
1. The in vitro basal lipid metabolism of rat pancreatic fragments was compared with that in adipose tissue fragments and liver slices. 2. [1-14C]Acetate added to the media was mostly incorporated into palmitic acid and to a lesser extent into oleic acid. In addition, pancreatic tissue exhibited a marked capacity for elongation of polyunsaturated fatty acids by [1-14C]acetate and resulting desaturation when compared to adipose tissue and liver. 3. Data obtained in the presence of [U-14C]glucose, [1-14C]palmitate and 3H20 indicate that acetyl-CoA derived from glucose and from beta-oxidation of fatty acids contributed to de novo lipogenesis. 4. Oxidation of [1-14C]palmitic acid was 9-13 times higher in the pancreas than in adipose tissue or liver when expressed on a wet weight basis. 5. The fatty acid moiety of pancreatic glycerolipids could be derived from de novo synthesis, fatty acids added to the medium, or from fatty acids formed from the hydrolysis of endogenous lipids. The glycerol moiety could be derived either from glucose, or directly from glycerol through participation of glycerol kinase.


Diagnosis and grading of chronic pancreatitis by morphological criteria derived by ultrasound and pancreatography.
The most commonly used modalities in the diagnosis of chronic pancreatitis are ultrasonography, computed tomography (CT) and endoscopic retrograde pancreatography (ERP). Computed tomography scanning is only of value in severe chronic pancreatitis. Both ultrasound and pancreatography are capable of showing ductal changes in mild forms of the disease, but comparison of the two methods has been difficult. A scheme of morphological criteria and descriptive terminology of pancreatitis was applied to 58 out of 85 patients with a firm clinical diagnosis of chronic pancreatitis. Twenty-seven patients were excluded from the study, four with a faulty clinical diagnosis and 23 with non-diagnostic pancreatograms. There was an exact classification into normal, equivocal, mild, moderate or marked chronic pancreatitis in 50 out of 58 patients (86%) and an almost perfect correlation (+ or - one grade) in 54 out of 58 (93%). There were four discrepancies. Ultrasound examination missed focal pancreatitis in the tail, a small cavity in the uncinate process and a variant of chronic pancreatitis. One ultrasound scan was of poor quality. Morphological grading by different techniques is feasible and use of this scheme can reduce diagnosis to a simple and specific set of rules.


Topology of glutathione-insulin transhydrogenase in rat liver microsomes.
Glutathione-insulin transhydrogenase (EC 188.8.131.52) catalyzes the inactivation of insulin through scission of the disulfide bonds to form insulin A and B chains. In the liver, the transhydrogenase occurs primarily in the microsomal fraction where most of the enzyme is present in a latent ('inactive') state. We have isolated rat hepatic microsomes with latent transhydrogenase activity being an integral part of the vesicles. We have used these vesicles to study the topological location of glutathione-insulin transhydrogenase by investigating the effects of detergents (Triton X-100 and sodium deoxycholate), phospholipase A2 and proteinases (trypsin and thermolysin) on the latent enzyme activity. Treatment of intact vesicles with variable concentrations of detergents and phospholipase A2 resulted in the unmasking of latent transhydrogenase activity. The extent of unmasking of transhydrogenase activity is dependent upon the concentration of detergent or phospholipase used and is accompanied by a parallel release of the enzyme into the soluble fraction. Activation of the transhydrogenase by phospholipase A2 is partially inhibited by bovine serum albumin and the extent of inhibition is inversely proportional to the phospholipase concentration. In intact vesicles, latent transhydrogenase activity is resistant to proteolytic inactivation by both trypsin and thermolysin, while in semipermeable and permeable vesicles these proteases inactivate 60 and 25% of the total transhydrogenase activity, respectively. Together these results indicate that in microsomes transhydrogenase is probably weakly bound to membrane phospholipid components and that most of the enzyme is present on the cisternal surface (i.e., the luminal surface of the endoplasmic reticulum) of microsomes. Each detergent and phospholipase apparently unmasks glutathione-insulin transhydrogenase activity through disruption of the phospholipid-enzyme interaction followed by translocation of the enzyme to the soluble (cytoplasmic) fraction and not through increases in substrate availability.


Molecular evolution of CXCR1, a G protein-coupled receptor involved in signal transduction of neutrophils.
Human neutrophils are a type of white blood cell, which forms an early line of defense against bacterial infections. Neutrophils are highly responsive to the chemokine, interleukin-8 (IL-8) due to the abundant distribution of CXCR1, one of the IL-8 receptors on the neutrophil cell surface. As a member of the GPCR family, CXCR1 plays a crucial role in the IL-8 signal transduction pathway in neutrophils. We sequenced the complete coding region of the CXCR1 gene in worldwide human populations and five representative nonhuman primate species. Our results indicate accelerated protein evolution in the human lineage, which was likely caused by Darwinian positive selection. The sliding window analysis and the codon-based neutrality test identified signatures of positive selection at the N-terminal ligand/receptor recognition domain of human CXCR1.


Management options for proximal humerus fractures - A systematic review & network meta-analysis of randomized control trials.
The purpose of this study is to systematically review the randomized controlled trials on the various treatment options that can be utilized in the management of displaced proximal humerus fractures. Based on the PRISMA guidelines, three independent reviewers performed a systematic review of the literature. Randomized control trials (RCTs) focusing on the outcomes of the following interventions in the management of PHFs were considered for inclusion; (1) non-operative or conservative (NOC) management, (2) open reduction and internal fixation (ORIF), (3) intra-medullary nailing (IMN), (4) shoulder hemi-arthroplasty (HA), and (5) reverse shoulder arthroplasty (RSA). Network meta-analyses were performed using R and studies were ranked according to their P-score. Our study included 13 RCTs. RSA had improvements in abduction, constant score, flexion, as well as lowest rates of malunion and osteonecrosis when compared to other management modalities (P-Score = 0.9786, P-Score = 0.9998, P-Score = 0.9909, P-Score = 0.9590 and P-Score = 0.8042 respectively). HA was found to have improvements in health-related quality of life scores when compared to other management modalities (P-Score = 0.9672). ORIF had the highest improvement in quick disability of arm, shoulder and hand scores and visual analogue scale scores (P-Score = 0.8209 and P-Score = 0.7155 respectively). NOC was found to have the lowest rate of conversion to surgical intervention, with RSA having the lowest rate of surgical interventions (P-Score = 0.9186 and P-Score = 0.7497 respectively). RSA offers satisfactory improvements in clinical and functional outcomes when compared to other non-operative and operative treatment options in the management of carefully selected proximal humerus fractures, with a minimal revision rate when compared to other surgical management modalities. I - Systematic Review & Meta-Analysis of Randomized Control Trials.


Association of the gut microbiome with cancer immunotherapy.
Immune checkpoint inhibitors, programmed cell death-1- and cytotoxic T-lymphocyte-associated protein 4-based immunotherapy have remarkably improved survival with durable response for patients with multiple cancer type. The accurate predictors of response and toxicity to immunotherapy are still unclear and have been focused on the gut microbiome. The gut microbiome, which refers to the microorganisms and their genes, affects the host immunity both locally and systemically. Modulation of the gut microbiota alters the immune systems and affects the efficacy of immune checkpoint inhibitor. In this review, we investigate the evidence on the role of the microbiome in cancer patients and discuss the impact of microbiome on the efficacy of immune checkpoint inhibitors in cancer.


Serine derived NK1 antagonists. 2: A pharmacophore model for arylsulfonamide binding.
Modifications to the spirocyclic aryl sulfonamide portion of serine derived NK1 antagonists allow a partial pharmacophore model to be developed.


Neonatal thrush of newborns: Oral candidiasis?
Neonatal thrush, also called oral candidiasis, is commonly a clinical diagnosis based on white patches on oral mucosal surfaces. Candida albicans is often associated with it. This clinical study aimed to investigate the presence of C. albicans among newborns with or without clinical findings of candidiasis on oral mucosa. Another aim was to investigate how thrush responded to current therapy by acidic liquids such as lingonberry or lemon juice. Swipe samples were collected from 32 healthy, full-term infants younger than 12 months with or without white patches on oral mucosa. Clinical diagnosis of thrush was made by a community nurse based on thick and yellowish white patches. The routine therapy was oral lingonberry or lemon juice or soda water. Disappearing of patches was controlled by a phone call about 2 weeks after the baseline. Both parents and nurses gave background factors by filling a questionnaire. One (3%) infant without clinical signs was diagnosed with Candida parapsilosis, none with C. albicans. Thrush resembling candidiasis was diagnosed clinically in four (12.5%) children. Three out of four parents reported persisting findings after 2 weeks. Only the maternal mastitis and use of antibiotics were significantly associated with thrush (p = .001). C. albicans was not discovered from babies with clinical thrush. Aetiology of the white patches remained unclear. The current way of treating them with acidic liquids is not efficient. Additional studies are needed.


Mitofusin2 Promotes β Cell Maturation from Mouse Embryonic Stem Cells via Sirt3/Idh2 Activation.
β cell dysfunction is the leading cause of diabetes. Adult β cells have matured glucose-stimulated insulin secretion (GSIS), whereas fetal and neonatal β cells are insensitive to glucose and are functionally immature. However, how β cells mature and acquire robust GSIS is not fully understood. Here, we explored the potential regulatory proteins of β cell maturation process and the capacity for GSIS. Combined with the data from public databases, we found that the gene expression of Mitofusin2 (Mfn2) showed an increasing trend from mouse neonatal β cells to mature β cells. Moreover, its protein expression increased during mouse embryonic pancreas development and β cell differentiation from mouse embryonic stem cells. Knocking down Mfn2 reduced Urocortin3 (Ucn3) expression, GSIS, and ATP production in induced β cells, while overexpressing it had the opposite effect. However, neither Mfn2 knockdown nor overexpression affected the differentiation rate of insulin-positive cells. In immature and mature β cells, Mfn2 and its correlated genes were enriched in tricarboxylic acid (TCA) cycle-related pathways. The expressions of Sirtuin 3 (Sirt3) and isocitrate dehydrogenase 2 (NADP+) and mitochondrial (Idh2) were Mfn2-regulated during β cell differentiation. Inhibiting Idh2 or Sirt3 reduced cellular ATP content and insulin secretion levels that increased by Mfn2 overexpression. Thus, Mfn2 modulated the induced β cell GSIS by influencing the TCA cycle through Sirt3/Idh2 activation. We demonstrated that Mfn2 promoted embryonic stem cell-derived β cell maturation via the Sirt3/Idh2 pathway, providing new insights into β cell development. Our data contribute to understanding diabetes pathogenesis and offer potential new targets for β cell regeneration therapies.


The effect of different growing conditions on water relations parameters of leaf epidermal cells of Tradescantia virginiana L.
Tradescantia virginiana L. plants were cultivated under contrasting conditions of temperature, humidity, light quality and intensity, and nutrient status in order to investigate the effect of growth conditions on the water relations parameters of the leaf epidermal cells. Turgor pressure (P), volumetric elastic modulus (ɛ), half-time of water potential equilibration (T 1/2), hydraulic conductivity (L p ) were measured with the miniaturized pressure probe in single cells of the upper and lower epidermis of leaves. Turgor differed (range: 0.1 bar to 7.2 bar) between treatments with lowest values under warm and humid conditions and additional supply of fertilizer, and highest values under conditions of low air humidity and low nutrient supply. The volumetric elastic modulus changed by 2 orders of magnitude (range: 3.0 bar to 350 bar, 158 cells), but ɛ was only affected by the treatments, in as much as it was dependent on turgor. The turgor dependence of ɛ, measured on intact leaves of T. virginiana, was similar to that for cells of the isolated (peeled) lower epidermis, where ɛ as a function of turgor was linear over the whole range of turgors. This result has implications for the discussion of pressure/volume curves as measured by the pressure bomb where changes in "bulk leaf ɛ" are frequently discussed as "adaptations" to certain treatments. The measurements of the hydraulic conductivity indicate that this parameter varies between treatments (range of means: 2.4×10-6 cm s-1 bar-1 to 13.4×10-6 cm s-1 bar-1). There was a negative correlation for L p in cells of intact leaves as a function of turgor which was altered by the growing conditions. However, a correlation with turgor could not be found for cells from isolated epidermis or cells from a uniform population of plants. The large variation in L p from cell to cell observed in the present and in previous studies was accounted for in a study of 100 cells from a uniform population of plants by the propagation of measurement errors in calculating L p . The results suggest that in T. virginiana cellular water relations are changed mainly by the turgor dependence of ɛ.


CD147 supports paclitaxel resistance via interacting with RanBP1.
Though the great success of paclitaxel, the variable response of patients to the drug limits its clinical utility and the precise mechanisms underlying the variable response to paclitaxel remain largely unknown. This study aims to verify the role and the underlying mechanisms of CD147 in paclitaxel resistance. Immunostaining was used to analyze human non-small-cell lung cancer (NSCLC) and ovarian cancer tissues. RNA-sequencing was used to identify downstream effectors. Annexin V-FITC/propidium iodide and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect apoptosis. Co-immunoprecipitation (Co-IP), fluorescence resonance energy transfer (FRET) and surface plasmon resonance (SPR) were performed to determine protein interactions. Fluorescence recovery after photobleaching (FRAP) was performed to measure the speed of microtubule turnover. Xenograft tumor model was established to evaluate sensitivity of cancer cells to paclitaxel in vivo. In vitro and in vivo assays showed that silencing CD147 sensitized the cancer cells to paclitaxel treatment. CD147 protected cancer cells from paclitaxel-induced caspase-3 mediated apoptosis regardless of p53 status. Truncation analysis showed that the intracellular domain of CD147 (CD147ICD) was indispensable for CD147-regulated sensitivity to paclitaxel. Via screening the interacting proteins of CD147ICD, Ran binding protein 1 (RanBP1) was identified to interact with CD147ICD via its C-terminal tail. Furthermore, we showed that RanBP1 mediated CD147-regulated microtubule stability and dynamics as well as response to paclitaxel treatment. These results demonstrated that CD147 regulated paclitaxel response by interacting with the C-terminal tail of RanBP1 and targeting CD147 may be a promising strategy for preventing paclitaxel resistant.


Occurrence and persistence of enteric viruses, arsenic and biotoxins in Pacific oysters farmed in an Italian production site.
The presence of Norovirus (NoV) and Hepatitis E virus (HEV) in non-depurated and depurated oysters raised in the north-west Italian coast was investigated by quantitative real-time RT-PCR. Total and inorganic arsenic (As) and the presence of marine biotoxins (DSP, ASP, PSP) by LC-MS were also investigated. NoV was detected through all the sampling period in non depurated and depurated oysters with highest levels during wintertime (>104 genome copies per gram, gc/g) and minimum values in summer below the LOQ (<130/140 gc/g). HEV has never been found as well as biotoxins. Total As concentration was found in oysters in the range 0.45-3.0 mg/kg, while inorganic As was found in all samples in concentrations below the LOQ (<0.020 mg/kg). The study highlights how the 24 h depuration process didn't reduce significantly NoV levels and therefore the high concentration of NoV in oysters could represent a risk for consumers especially during winter and spring months.


Interleukin-4 activates the PI3K/AKT signaling to promote apoptosis and inhibit the proliferation of granulosa cells.
The inflammatory microenvironment has been demonstrated to play a role in folliculogenesis, ovulation and premature ovarian failure (POF), as well as infertility. In this study, we aimed to explore the role of inflammation in modulating growth and apoptosis in granulosa cells (GCs), the main components of ovarian follicles. ELISA was used to analyze the levels of inflammatory factors (IL-1β, IL-4, IL-6 and IL-10) in follicular fluid samples and GCs derived from POF patients and healthy normal individuals. CCK-8, flow cytometry and TUNEL assays were used to assess the effect of IL-4 on GC growth and apoptosis. Western blotting was used to examine the effect of IL-4 on the activation of PI3K/Akt, Erk1/2 and Jnk signaling. The results showed that IL-4, IL-1β and IL-6 levels were increased in follicular fluid samples and GCs derived from POF patients compared with those from healthy individuals. GC growth was weakened when cells were treated with IL-4, while apoptosis was increased. In addition, IL-4 increased the level of p-Akt/Akt in GCs. In addition, LY294002, an inhibitor of PI3K, abolished the effect of IL-4 by inhibiting GC growth and promoting apoptosis. In summary, this study demonstrated that IL-4 levels were increased in POF samples and that IL-4 could inhibit GC growth and induce GC apoptosis by activating PI3K/Akt signaling.


Oral follicular lymphomas. A short report of 8 cases with assessment of the IGH/BCL2 gene fusion with fluorescence in situ hybridization.
To present the clinicopathologic features and confirm the presence of the IGH/BCL2 gene fusion in an oral follicular lymphoma (OFL) series. Cases of OFLs were retrieved from a data base of non-Hodgkin lymphomas (NHL). Fluorescence in situ hybridization (FISH) was performed to confirm the IGH/BCL2 fusion. Eight (8.7%) of 92 NHL were OFLs. Six (75%) patients were male and two female (mean age: 73.4 ± 14.8). The most frequent site was the palate. Five of the 8 patients are alive and without disease. Five (three grade 1 and two grade 2) of six successfully hybridized cases revealed the IGH/BCL2 gene fusion. The sixth case, a grade 3 follicular lymphoma (FL), demonstrated multiple BCL2 signals without IGH/BCL2 fusion. OFLs exhibit an indolent clinical behavior. In the present study, 5/6 cases in which FISH was successful had an IGH/BCL2 fusion as would result from the t(14; 18)(q32; q21) translocation commonly seen in FL of extraoral sites.


Synthesis and characterization of aminated lignin.
Amination of lignin can bring reactive amino groups onto the natural polymer and enable it to be employed in engineering materials. The amination reaction was successfully implemented after some of the hydroxyl groups on lignin were epoxidized. The resulted products showed a great quantity of primary amine group and secondary amine group which can be used as curing agents of epoxy resin. The results revealed that several factors including reaction temperature and time, as well as ratios of compounds, could influence the epoxidation and amination reactions. The resulted products were characterized by FT-IR spectra, (1)H NMR, (13)C NMR, element analysis, XPS and thermogravimetry analysis.


The 'Jack Stone' or 'Mercedes Benz' sign--anew theory to explain the presence of gas within fissures in gallstones.
Gas within clefts of fissures in gallstones is not a very common finding, but when it occurs is, characteristic and indicates the presence of one or more calculi. It closely resembles the appearance of a 'Jack Stone' but has previously been termed the 'Mercedes Benz' sign. Only a few cases have previously been recognised in the U.K. Most reported cases have been associated with biliary colic or cholecystitis. Various theories have been put forward to explain the presence of gas, but the author believes that the gas is released from solution by negative pressure within cholesterol stones undergoing internal fissuring due to their crystalline structure, i.e. the gas is released from solution from the small amount of fluid trapped in the calculus, in the same way that gas may be 'pulled' out of solution in a joint, a degenerate intervertebral disc or the fibro-cartilage of the symphysis pubis.


Myalgia and biochemical changes following intermittent suxamethonium administration. Effects of alcuronium, lignocaine, midazolam and suxamethonium pretreatments on serum myoglobin, creatinine kinase and myalgia.
One hundred gynaecological patients for laparoscopy divided into five groups were studied to determine the effects of a number of pretreatments on serum myoglobin, creatinine kinase and myalgia following intermittent suxamethonium administration. One group acted as controls, while the other groups were given intravenous pretreatments of alcuronium 2 mg, midazolam 0.15 mg/kg, lignocaine 1.5 mg/kg and suxamethonium 7 mg. Serum myoglobin was determined by radio-immunoassay. The mean increases in the control group were 167 micrograms/litre myoglobin at 20 minutes and 196 IU creatinine kinase at 24 hours; 13 out of 20 patients responded with a marked increase of serum myoglobin at 20 minutes and of creatinine kinase at 24 hours. Only alcuronium pretreatment prevented myoglobin increase at 20 minutes, abolished creatinine kinase increase at 24 hours and reduced 24-hour myalgia. The other pretreatments slightly reduced myoglobin increase at 20 minutes and 24-hour creatinine kinase but did not reduce myalgia. Only one patient in the whole study had markedly elevated serum myoglobin at 24 hours. We conclude that only non-depolarising relaxant pretreatment is effective in the reduction of some of the adverse effects of suxamethonium administration.


Preparation of metallized GaN/sapphire cross sections for TEM analysis using wedge polishing.
The tripod polisher has been used successfully in the past, in the preparation of difficult Si-based TEM cross-section specimens. Good TEM specimens, with large electron transparent areas, can be prepared in a relatively short time. In addition, wedge polishing considerably reduces the ion milling time because of the thinness of the final specimen. For metallized GaN on sapphire substrates, there are problems not inherent to Si-based materials: (1) sapphire is a difficult material to thin due to its high hardness and its mechanical instability when thinned below 20 m; (2) delamination of metal layers from the GaN can occur during polishing and/or ion milling; (3) markedly different ion milling rates for the metals and semiconductors. In this paper, wedge polishing has been modified to make it suitable for preparation of metallized GaN/sapphire samples or other metallized semiconductors and ceramics for TEM analysis. Using this method, TEM cross section specimens can be prepared with reasonably large thin areas.


A Platform for Addressing Individual Magnetite Islands Grown Epitaxially on Ru(0001) and Manipulating Their Magnetic Domains.
We have grown high-quality magnetite micrometric islands on ruthenium stripes on sapphire through a combination of magnetron sputtering (Ru film), high-temperature molecular beam epitaxy (oxide islands), and optical lithography. The samples have been characterized by atomic force microscopy, Raman spectroscopy, X-ray absorption and magnetic circular dichroism in a photoemission microscope. The magnetic domains on the magnetite islands can be modified by the application of current pulses through the Ru stripes in combination with magnetic fields. The modification of the magnetic domains is explained by the Oersted field generated by the electrical current flowing through the stripes underneath the magnetite nanostructures. The fabrication method is applicable to a wide variety of rock salt and spinel oxides.


Three-dimensional magnetic resonance-based morphometrics and ventricular dysmorphology in schizophrenia.
Recent methodological refinements in magnetic resonance (MR) imaging have led to brain averaging and morphometric approaches that are sensitive to subtle anatomical distinctions in schizophrenia. Using a novel morphometric technique for surface analysis, 48 selected landmarks of the rendered ventricular system were extracted and compared between the ventricles of 20 patients with schizophrenia and 20 normal subjects. There was no significant difference in ventricular shape between groups, but significant (p = .015) and highly localized shape deformity was detected at the foramen of Monro and at the proximal temporal horn of the lateral ventricle of male (but not female) patients relative to controls. Three-dimensional MR-based morphometrics complements established volumetric approaches and can detect minute shape deformities that may be associated with schizophrenia.


The miRNA let-7a1 inhibits the expression of insulin-like growth factor 1 receptor (IGF1R) in prostate cancer PC-3 cells.
Reduced microRNA (miRNA) let-7a expression and the activation of insulin-like growth factor-1 receptor (IGF1R) signalling are both involved in prostate cancer and progression. In the present study, we demonstrated that the growth inhibitory effect of let-7a1 is directly related to targeting IGF1R gene expression in PC-3 cells. TargetScan predicted three potential target sites (T1, T2 and T3) of let-7a in the 3' untranslational region (3' UTR) of IGF1R mRNA. Real-time PCR, Western blot and luciferase reporter assays were used to detect the effects of let-7a1 overexpression or let-7a1 inhibitor on the IGF1R gene expression in PC-3 cells. The results indicated that let-7a1 could inhibit IGF1R expression by directly targeting the T1 and T2 sites in the 3' UTR of the IGF1R mRNA. We then used RT-PCR, luciferase reporter assays, 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry and Hoechst 33342 staining to examine whether let-7a1-mediated inhibition of IGF1R expression also affects the IGF1R-mediated signalling events, including Elk1 activity and c-fos gene expression, proliferation, apoptosis and cell cycle. We demonstrated that let-7a1-mediated IGF1R downregulation was accompanied by attenuation of Elk1 activity and c-fos expression, inhibition of cell proliferation, enhanced apoptosis and cell cycle arrest, and that loss function of let-7a1 via inhibition can upregulate IGF1R accompanied by an increase of Elk1 activity and c-fos expression, thereby enhancing cell proliferation. Altogether, these findings suggest that let-7a may be novel therapeutic candidate for prostate cancer.


Interindividual influence on diurnal rhythms of activity in cycling and noncycling populations of the field vole, Microtus agrestis L.
The effects of interaction among individuals with respect to wheelrunning activity has been investigated in two geographically separated populations of the field vole Microtus agrestis L. In one of them, a northern cyclically varying population, a strictly nocturnal activity pattern is changed into a more or less short term 24 h pattern under conditions of increased contact among individuals. In the other population, south-Swedish, without population cycles, no such effects were observed. This indicates population differences in response to interindividual contact which might be of importance to the known differences in population dynamics.


Prevalence of vertebral fractures in children with chronic rheumatic diseases at risk for osteopenia.
To determine the prevalence of and the risk factors for vertebral fractures in a cohort of children with chronic rheumatic diseases considered at risk for osteopenia. We conducted a cross-sectional study of patients with chronic rheumatic diseases at the Montreal Children's Hospital. Of the 90 study participants (22 boys, 68 girls), 10 boys and 7 girls (19%) were found to have vertebral fractures. These 17 children had a total of 50 fractures, an average of 2.9 per affected child. Fractures in the upper thoracic region (T5-8) accounted for 55%. Only 56% of all fractures were symptomatic. With multivariate regression, we identified male sex (P < .01), body mass index z-score (P < .02), and cumulative glucocorticoid dose (P < .01) as significant predictors of the number of vertebral fractures. Our study examined the prevalence of vertebral fractures in a high-risk pediatric population. Nineteen percent of our cohort had vertebral fractures. Significant risk factors for the development of vertebral fractures include male sex and cumulative glucocorticoid dose. Better understanding of the extent of the problem in this population will allow us to further refine screening guidelines and treatment in these patients.


Mechanisms of neurotoxicity and their relationship to behavioral changes.
In this review some of the evidence relating behavioral alterations induced by 2 neurotoxic chemicals, lead acetate and methyl mercury is presented with an attempt to relate these changes to the underlying neurobiological mechanisms. In the case of neonatal lead poisoning, the results of the early behavioral studies were confounded by excessive lead concentrations resulting in undernutrition of the pups. Subsequent studies in both rodents and monkeys have shown that blood-lead concentrations comparable to those seen in children can induce behavioral alterations that may be related to hippocampal damage. In the case of methyl mercury which is a potent cytotoxic agent, prenatal exposure results in widespread cortical, and cerebellar alterations characterized by reduced myelination, delayed migration and loss of neurons. These morphological alterations are accompanied by permanent alterations in learning and memory as well as altered pharmacological sensitivity in catecholaminergic systems. Recommendations are made for better formulated behavioral and neurobiological assays in neurotoxicology in order to lead to a better understanding of the toxicity of chemicals.


Disparities in Diagnostic Imaging for Initial Local Staging for Rectal Cancer.
To assess the presence, quality, and timeliness of initial staging imaging for rectal cancer patients, and to evaluate demographic factors associated with disparities. We conducted a chart review of consecutive rectal adenocarcinoma cancer registry cases from a single institution for the period from 2015 to 2020. We recorded whether initial staging MRI or endoscopic ultrasound (EUS) was performed, and whether it was performed in or outside the institution. MRI quality was assessed based on compliance to the Society of Abdominal Radiology rectal cancer disease-focused panel protocol recommendations. The times between diagnosis and imaging were calculated. Patients' age, race, ethnicity, sex, body mass index, address, and primary payer were acquired from the electronic medical record. Descriptive analysis, odds ratios, and t-tests were used for analysis. Of 346 patients, 39% were female, and the average age was 59 years. A total of 93 patients (26.8%) had no initial staging MRI or endoscopic ultrasound. Of the 142 MRIs evaluated for image quality, 100 patient exams (72.4%) met the criteria for adequate quality. The mean time interval from diagnosis to imaging was 30.9 days. A lower likelihood of receiving initial local staging was associated with being of Hispanic ethnicity (P < .01), having Medicaid or no insurance (P < .01), and residing in a low-income census block (P < .01). Higher quality of imaging was associated with residence in a census block with high median income (P < 0.01), more recent diagnosis (P < .01), and MRI performed at the institution presented (P < .01). Although radiologic workup variability was found across all demographics, sociodemographic factors have an effect on local initial imaging of rectal cancer, emphasizing the need to improve image acquisition for underserved patients and improve quality standardization at low-volume centers.


Identifiability of species network topologies from genomic sequences using the logDet distance.
Inference of network-like evolutionary relationships between species from genomic data must address the interwoven signals from both gene flow and incomplete lineage sorting. The heavy computational demands of standard approaches to this problem severely limit the size of datasets that may be analyzed, in both the number of species and the number of genetic loci. Here we provide a theoretical pointer to more efficient methods, by showing that logDet distances computed from genomic-scale sequences retain sufficient information to recover network relationships in the level-1 ultrametric case. This result is obtained under the Network Multispecies Coalescent model combined with a mixture of General Time-Reversible sequence evolution models across individual gene trees. It applies to both unlinked site data, such as for SNPs, and to sequence data in which many contiguous sites may have evolved on a common tree, such as concatenated gene sequences. Thus under standard stochastic models statistically justifiable inference of network relationships from sequences can be accomplished without consideration of individual genes or gene trees.


DECOLONIZING CANCER CARE IN CANADA.
Cancer incidence and mortality among Indigenous peoples of Canada (First Nations, Inuit, and Métis) continue to rise in contrast to non-Indigenous Canadians, and Indigenous peoples are at higher risk of cancers associated with known modifiable risk factors. Jurisdictional and administrative challenges have hindered high quality cancer care for Indigenous peoples since the country's inception, and different Indigenous populations face these challenges under similar yet non-identical circumstances. Collaborative initiatives under Indigenous leadership have drawn attention to specific issues such as screening, funding, and culturally appropriate care, and have identified resources necessary to address these problems. The Canadian Partnership Against Cancer and their collaborators have committed significant resources to Indigenous cancer programs with locally and regionally determined leadership and priorities. In the context of broader global movements against systemic racism and inequity, decolonization of cancer care demands critical analysis of the existing cancer systems and restructuring under Indigenous leadership with multidisciplinary collaboration.


The prevalence of abnormal right ventricle speckle strain in the setting of acute myocarditis and preserved left ventricle function.
Acute myocarditis has a wide spectrum of clinical presentation, from subclinical disease to acute heart failure, and sudden cardiac death. Two-dimensional speckle tracking echocardiography (2D-STE) has been proven effective in early diagnosis of subclinical cardiac injury, however, there is a limited data regarding the right ventricle (RV) involvement among patients with acute myocarditis. We evaluated the prevalence of early subclinical RV injury assessed by 2D-STE, among patients with acute myocarditis and preserved left ventricle (LV) function. We performed a retrospective single-center study at Tel-Aviv Sourasky Medical Center, including all adult patients hospitalized with acute myocarditis, who presented with preserved LV function. 2D-STE analysis of the RV was performed offline, assessing both the RV four-chamber longitudinal strain peak systolic (RV4CLS PK) and the free wall longitudinal strain peak systolic (RVFWLS PK). The myocarditis group was compared to a healthy control group. From 2011 to 2020, a total of 90 patients included in the study and were compared to 70 healthy subjects. RV 2D-STE emerged as significantly lower for both the RV4CLS PK (-21.8 ± 4.2 vs. -24.9 ± 4.8, P < 0.001) and RVFWLS PK (-24.7 ± 4.9 vs. -28.4 ± 5, P < 0.001), and remained significant in a multivariate analysis. We presented for the first time the presence of subclinical RV dysfunction, assessed by 2D-STE, in patients diagnosed with acute myocarditis, in the presence of preserved LV function. Further studies are needed to evaluate its' role in the development of LV dysfunction, heart failure and mortality.


A survey of the methods used by farmers to castrate calves in New Zealand.
To identify the methods used to castrate calves and the age at which castration is carried out on farms in New Zealand. A survey was carried out by questionnaire sent to the 14,000 recipients of Meat Matters produced by Meat New Zealand. The questionnaires on return were analysed on a national and regional basis. Of the 3,788 respondents, 74% (2,825) castrated calves on their farms. Of these 2,825 respondents 85% (2,403) used a rubber ring, 18% (512) carried out surgical castration and only a few respondents, 25, used a clamp. The ring was used on calves with an average age of 2.2 months and 93% of calves castrated by ring were castrated during the first 3 months of life. Surgical castration was carried out on calves with an average age of 4.3 months, 54% of them were castrated in the first 3 months of life and 39% during the following 3 months. Respondents from the West Coast (40%), Otago (38%) and Southland (50%) were more likely to use surgical castration than respondents from elsewhere (<17%). Local anaesthetic was used by only 3% (94) of respondents and a similar percentage employed a veterinarian to do the castration. There are marked regional differences in methodology used for castration of calves. The survey gives a sound basis for future research into humane and cost effective methods.


Precision of individual and composite performance scores: the ideal number of indicators in an indicator set.
In many countries, quality indicators are used to assess the quality of care of family practice. Such assessments need to have an adequate precision, so that the results can be interpreted correctly. However, a small sample size per practitioner can lead to inadequate precision. A possible solution could be to create composite performance scores. To evaluate the relationship between sample size and precision. We examine whether a composite performance score has an increased precision and how many indicators are needed minimally to achieve this level of precision. We performed a descriptive statistical study on data from the medical records of 455 Dutch practices. We included 3 different conditions: diabetes (12 indicators), chronic obstructive pulmonary disease (4 indicators), and Cardiovascular Disease and Risk Management (9 indicators). For individual quality indicators, patient samples close to 100 are required to achieve even moderate precision (10 percentage points) on the performance scores. This number decreases substantially when a composite score is used. A composite derived from combining 5 to 7 indicators can provide much the same precision of measurement as one made up from a much larger number of indicators. The added value of a composite score depends on the a priori reasons for measuring quality. Our results indicate that especially for formative quality improvement a small number of carefully selected indicators can provide a sufficiently precise composite measure.


High-frequency repetitive transcranial magnetic stimulation delays rapid eye movement sleep.
Repetitive transcranial magnetic stimulation (rTMS) is a promising new treatment for patients with major depression. However, the mechanisms underlying the antidepressive action of rTMS are widely unclear. Rapid eye movement (REM) sleep has been shown to play an important role in the pathophysiology of depression. In the present study we demonstrate that rTMS delays the first REM sleep epoch on average by 17 min (102.6 +/-22.5 min vs 85.7+/-18.8 min; p < 0.02) and prolongs the nonREM-REM cycle length (109.1+/-11.4 min vs 101.8+/-13.2min, p< 0.012). These rTMS-induced changes in REM sleep variables correspond to findings observed after pharmacological and electroconvulsive treatment of depression. Therefore, it is likely that the capability of rTMS to affect circadian and ultradian biological rhythms contributes to its antidepressive action.


Antisera to synthetic peptides as probes of structural changes during aging of alpha-crystallin from the bovine lens.
Polyclonal antisera have been made to synthetic peptides of 11-15 residues that correspond to nine different regions of the alpha A crystallins. These antisera have been used in a radioimmunoassay to quantitatively probe for structural and/or covalent changes of alpha-crystallins in the nucleus versus cortex of the adult bovine lens. Antisera specific for the C-terminal and N-terminal regions of the alpha-crystallins bind more to alpha-crystallins from cortex. Antisera to three out of the seven internal sequences (residues 75-89, 87-101 and 135-149) bind better to alpha-crystallins from the bovine lens nucleus, suggesting a greater accessibility of these sequences to antisera binding. Together, these studies demonstrate that antisera against synthetic peptide sequences of alpha A crystallins are very specific probes that can detect structural and/or covalent changes in specified regions of the alpha-crystallins during the process of aging in the bovine lens.


Dataset for the analysis of gendered research productivity affected by early COVID-19 pandemic.
In many countries, COVID-19 has made it harder for women to study because they are expected to do more housework and care for children. This article encompasses different data sources that can be used to figure out how the early pandemic of COVID-19 affected the number of studies done by females, in comparison with males. This data is add-on metadata that can be used with raw Microsoft Academic Graph (MAG) from 2016 to 2020 of the Feb 6, 2021 dump. We retrieved open-source metadata from various sources, including LinkedIn, the Johns Hopkins Coronavirus Resource Center, and Google's COVID-19 Community Mobility Reports, and linked bibliographic information to characteristics of the author's environments. It consists of published journals and online preprints, including each author's gender and involvement in the publication, their position through time, the h-index of their institutes, and gender equality in the professional labor market at the country level. For each record of papers, the data also includes the information of the papers, e.g., title and field of study. By gathering this evidence, our data can support the fact diversity in science is more than just the number of active members of different groups. It should also examine minority participation in science. Our data may help scholars understand diversity in science and advance it. The article ``The effect of the COVID-19 pandemic on gendered research productivity and its correlates'' uses this data as the principal source (Kwon, Yun & Kang, 2021).


Risk factors associated with postoperative intensive care unit delirium in patients undergoing invasive mechanical ventilation following acute exacerbation of chronic obstructive pulmonary disease.
This study was performed to determine the risk factors associated with intensive care unit delirium (ICUD) in patients undergoing invasive mechanical ventilation (IMV) secondary to acute exacerbation of chronic obstructive pulmonary disease (COPD). Data involving 620 patients undergoing IMV secondary to acute exacerbation of COPD from 2009 to 2019 at the First Hospital of Hebei Medical University were retrospectively analysed. The primary endpoint was the risk factors associated with developing ICUD. Univariable and multivariable logistic regression analyses were used to identify these risk factors. Of 620 patients, 93 (15.0%) developed ICUD. In the multivariable analysis, risk factors that were significantly associated with ICUD were increased age, male sex, alcoholism with active abstinence, current smoking, stage 3 acute kidney injury (AKI), and an American Society of Anesthesiologists (ASA) physical status of III. This study showed that increasing age, male sex, alcoholism with active abstinence, current smoking, stage 3 AKI, and an ASA physical status of III might be associated with a risk of developing ICUD. Even if these risk factors are unaltered, they provide a target population for quality improvement initiatives.


Differential effects of simian immunodeficiency virus infection on immune inductive and effector sites in the rectal mucosa of rhesus macaques.
The rectal mucosa, a region involved in human immunodeficiency virus/simian immunodeficiency virus (SIV) infection and transmission, contains immune inductive sites, rectal lymphoid nodules (RLN), and effector sites, the lamina propria (LP). This study was designed to evaluate cell populations involved in rectal mucosal immune function in both RLN and LP, by immunocytochemical analysis of rectal mucosa from 11 SIV-infected (2 to 21 months postinfection) and five naive rhesus macaques. In the rectum, as previously observed in other intestinal regions, CD4(+) cells were dramatically reduced in the LP of SIV-infected macaques, but high numbers of CD4(+) cells remained in RLN indicating maintenance of T cell help in inductive sites. Cells expressing the mucosal homing receptor alpha4beta7 were dramatically decreased in the RLN and LP of most SIV-infected macaques. The RLN of both naive and SIV-infected macaques contained high numbers of CD68 + MHC-II+ macrophages and cells expressing the co-stimulatory molecules B7-2 and CD40, as well as IgM + MHCII+ and IgM + CD40+ B cells, indicating maintenance of antigen presentation capacity. The LP of all three macaques SIV-infected for 2 months contained many B7-2+ cells, suggesting increased activation of antigen-presenting cells. LP of SIV-infected rectal mucosa contained increased numbers of IgM+ cells, confirming previous observations in small intestine and colon. The data suggest that antigen-presentation capacity is maintained in inductive sites of SIV-infected rectal mucosa, but immune effector functions may be altered.


The European Medicines Agency Review of Brentuximab Vedotin (Adcetris) for the Treatment of Adult Patients With Relapsed or Refractory CD30+ Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use.
On October 25, 2012, a conditional marketing authorization valid throughout the European Union (EU) was issued for brentuximab vedotin for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL) and for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). For HL, the indication is restricted to treatment after autologous stem cell transplantation (ASCT) or after at least two previous therapies when ASCT or multiagent chemotherapy is not a treatment option. Brentuximab vedotin is an antibody-drug conjugate (ADC) composed of a CD30-directed monoclonal antibody (recombinant chimeric IgG1) that is covalently linked to the antimicrotubule agent monomethyl auristatin E (MMAE). Binding of the ADC to CD30 on the cell surface initiates internalization of the MMAE-CD30 complex, followed by proteolytic cleavage that releases MMAE. The recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Brentuximab vedotin as a single agent was evaluated in two single-arm studies. Study SG035-003 included 102 patients with relapsed or refractory HL. An objective response was observed in 76 patients (75%), with complete remission in 34 (33%). Study SG035-004 included 58 patients with relapsed or refractory sALCL. An objective response was observed in 50 patients (86%), with complete remission in 34 (59%). The most frequently observed toxicities were peripheral sensory neuropathy, fatigue, nausea, diarrhea, neutropenia, vomiting, pyrexia, and upper respiratory tract infection. The present report summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of the product characteristics, are available on the European Medicines Agency website (http://www.ema.europa.eu). Brentuximab vedotin was approved in the European Union for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma or systemic anaplastic large cell lymphoma. For Hodgkin lymphoma, brentuximab vedotin should only be used after autologous stem cell transplantation or following at least two prior therapies when transplantation or multiagent chemotherapy is not a treatment option. In two studies involving 160 patients, partial or complete responses were observed in the majority of patients. Although there was no information on the survival of patients treated in the studies at the time of approval, the responses were considered a clinically relevant benefit.


Horse-Rider Pairing Perception by Dressage Judges and Equestrian Coaches.
The ideal equestrian body image (BI) is a smaller physique and riders feel body shape (BS) influences subjective judge scoring within dressage competitions. The aims were to identify perceptions of equestrian coaches and dressage judges of rider body shape (BS), identify perceptions of appropriate horse-rider matching and establish the impact of BS on perceived rider ability. An online survey (GoogleFormsTM) was shared, respondents (n = 265, coaches = 174 judges = 91) viewed images of twelve riders of different BS (Ectomorph, Mesomorph, and Endomorph) mounted on three horses of different breeds/types and asked to indicate the best horse-rider match. Judges were asked if body shape or inappropriate horse-rider matching influenced scores given, this was used to identify any bias from judges. A significant perception for horse rider matching identified the cob as the most appropriate for the Endomorph physique (P < .001). Ectomorph was the most chosen as the ideal BS on all horses. Both coaches and judges identified the ideal physique as a smaller image from the BI scale. Both coaches and judges individually perceive that BS impacts rider ability (P < .001). These findings of BS perceived as linked to rider skill potentially identifies an issue and may correspond to the smaller physique being idealistic. Future research into physique related bias from judges is required to further identify the impact of BS on subjective judging within equestrian sport.


Reduction of acid mine drainage by passivation of pyrite surfaces: A review.
Acid mine drainage (AMD), a source of considerable environmental pollution worldwide, has prompted the development of many strategies to alleviate its effects. Unfortunately, the methods available for remedial treatment of AMD and the damage it cause are generally costly, labor-intensive, and time-consuming. Furthermore, such treatments may result in secondary pollution. Alternatively, treating the AMD problem at its source through pyrite surface passivation has become an important topic for research because it has the potential to reduce or prevent the generation of AMD and associated pollution. This review summarizes various pyrite anti-corrosion technologies, including the formation of various passivating coatings (inorganic, organic and organosilane) and carrier-microencapsulation. Several effective long-term passivators are identified, although many of them currently have important deficiencies that limit their practical application. Combining the mechanisms of existing passivation agents or new artificial materials, while considering environmental conditions, costs, and long-term passivation performance, is a feasible direction for future research.


NPM1 exhibits structural and dynamic heterogeneity upon phase separation with the p14ARF tumor suppressor.
Nucleophosmin (NPM1) is an abundant nucleolar protein that aids in the maturation of pre-ribosomal particles and participates in oncogenic stress responses through its interaction with the Alternative Reading Frame tumor suppressor (p14ARF). NPM1 mediates multiple mechanisms of phase separation which contribute to the liquid-like properties of nucleoli. However, the effects of phase separation on the structure and dynamics of NPM1 are poorly understood. Here we show that NPM1 undergoes phase separation with p14ARF in vitro, forming condensates that immobilize both proteins. We probed the structure and dynamics of NPM1 within the condensed phase using solid-state NMR spectroscopy. Our results demonstrate that within the condensed phase, the NPM1 oligomerization domain forms an immobile scaffold, while the central intrinsically disordered region and the C-terminal nucleic acid binding domain exhibit relative mobility.


Zerovalent iron and iron(VI): Effective means for the removal of psychoactive pharmaceuticals and illicit drugs from wastewaters.
Herein we report the analysis of 27 selected psychoactive compounds found in the wastewater of the largest suburb in the eastern part of Central Europe Bratislava—Petržalka, Slovakia. Thirteen of them (MDMA, methamphetamine, amphetamine, THC-COOH, benzoylecgonine, codeine, tramadol, venlafaxine, oxazepam, citalopram, methadone, EDDP, cocaine) were found in concentrations above 30 ng/L. These compoundswere selected for further monitoring. The possibility of complete degradation of these 13 substances by zerovalent iron and iron(VI) was studied in thewastewater from the Petržalka treatment plant. During the week the concentration of themajority of the studied compounds inwastewaterwas stable. Concentrations of MDMA, cocaine, tramadol, and oxazepam reached significantly higher levels during the weekend.Only about 10% removal efficiency for tramadol, venlafaxine, oxazepam, MDMA, citalopram, methadone, and EDDP was observed at the treatment plant. In contrast, methamphetamine, amphetamine, and codeine were removed with 68%, 83%, and 53% efficiency, respectively. The degradation of synthetic drugs (methamphetamine, cocaine, MDMA) in wastewater is limited, while cannabis (of natural biological origin) is degradedwith efficiency greater than 90%. After utilization of the Fenton reaction, its modification, and use of ferrate(VI), a high efficiency of eliminating all of these substances to values below the limit of detection was achieved.


Mental health and well-being of fathers of children with intellectual disabilities: systematic review and meta-analysis.
Caring for a child with intellectual disabilities can be a very rewarding but demanding experience. Research in this area has primarily focused on mothers, with relatively little attention given to the mental health of fathers. The purpose of this review was to summarise the evidence related to the mental health of fathers compared with mothers, and with fathers in the general population. A meta-analysis was undertaken of all studies published by 1 July 2018 in Medline, PsycINFO, CINAHL and EMBASE, using terms on intellectual disabilities, mental health and father carers. Papers were selected based on pre-defined inclusion and exclusion criteria. Of 5544 results, 20 studies met the inclusion criteria and 12 had appropriate data for meta-analysis. For comparisons of fathers with mothers, mothers were significantly more likely to have poor general mental health and well-being (standardised mean difference (SMD) -0.38, 95% CI -0.56 to -0.20), as well as higher levels of depression (SMD, -0.46; 95% CI -0.68 to -0.24), stress (SMD, -0.32; 95% CI -0.46 to -0.19) and anxiety (SMD, -0.30; 95% CI -0.50 to -0.10). There is a significant difference between the mental health of father and mother carers, with fathers less likely to exhibit poor mental health. However, this is based on a small number of studies. More data is needed to determine whether the general mental health and anxiety of father carers of a child with intellectual disabilities differs from fathers in the general population.


Reconstruction techniques for energy-absorbing guardrail end terminals.
Steel beam longitudinal barriers protect errant vehicles from roadside hazards; when impacted, they safely redirect the impacting vehicle and minimize the probability of serious injury. Guardrail end terminals are devices placed on the ends of longitudinal barriers and are frequently hit by vehicles that leave the roadway. Crash reconstruction is the effort to determine how a vehicle crash has occurred. Reconstruction is performed by several groups, including designers and testers of roadside safety devices so that they design and test for real-world conditions, and also by departments of transportation in order to determine appropriate warrants, maximizing the benefit-cost ratio for limited resources. This paper focuses on two items: first, the numerous types of energy-absorbing guardrail end terminals are identified and delineated and second, a crash reconstruction technique for determining the initial velocity of a vehicle impacting a guardrail end terminal based upon conservation of momentum and conservation of energy is developed. By understanding the types of guardrail terminals and being able to reconstruct real-world crashes, highway planners, designers and maintenance people will have significant more information than is currently available to aid in the goal of mitigating roadside crashes.


Temporal bone CT findings in the CHARGE association.
Ten out of 20 cases with the CHARGE association and two CHARGE-like cases underwent temporal bone CT scanning and/or MRI: they all showed bilateral aplasia of the semicircular canals and obliteration of the oval windows. Vestibular examination was performed in nine CHARGE cases and the two CHARGE-like cases, which disclosed vestibular areflexia in all of them. Of the 16 evaluable CHARGE cases, eight had bilateral mixed hearing impairment, while eight had sensorineural hearing impairment which was bilateral in six and unilateral in two cases. Temporal bone CT scanning is therefore indicated in suspected CHARGE cases, even if they show normal hearing or a relatively good bone conduction threshold in one or both ears.


In vitro maturation of dopaminergic neurons derived from mouse embryonic stem cells: implications for transplantation.
The obvious motor symptoms of Parkinson's disease result from a loss of dopaminergic neurons from the substantia nigra. Embryonic stem cell-derived neural progenitor or precursor cells, adult neurons and fetal midbrain tissue have all been used to replace dying dopaminergic neurons. Transplanted cell survival is compromised by factors relating to the new environment, for example; hypoxia, mechanical trauma and excitatory amino acid toxicity. In this study we investigate, using live-cell fluorescence Ca(2+) and Cl(-) imaging, the functional properties of catecholaminergic neurons as they mature. We also investigate whether GABA has the capacity to act as a neurotoxin early in the development of these neurons. From day 13 to day 21 of differentiation [Cl(-)](i) progressively dropped in tyrosine hydroxylase positive (TH(+)) neurons from 56.0 (95% confidence interval, 55.1, 56.9) mM to 6.9 (6.8, 7.1) mM. At days 13 and 15 TH(+) neurons responded to GABA (30 µM) with reductions in intracellular Cl(-) ([Cl(-)](i)); from day 21 the majority of neurons responded to GABA (30 µM) with elevations of [Cl(-)](i). As [Cl(-)](i) reduced, the ability of GABA (30 µM) to elevate intracellular Ca(2+) ([Ca(2+)](i)) did also. At day 13 of differentiation a three hour exposure to GABA (30 µM) or L-glutamate (30 µM) increased the number of midbrain dopaminergic (TH(+) and Pitx3(+)) neurons labeled with the membrane-impermeable nuclear dye TOPRO-3. By day 23 cultures were resistant to the effects of both GABA and L-glutamate. We believe that neuronal susceptibility to amino acid excitotoxicity is dependent upon neuronal maturity, and this should be considered when isolating cells for transplantation studies.


2-Phenylpyridine ruthenacycles as effectors of glucose oxidase activity: inhibition by Ru(II) and activation by Ru(III).
Cyclometalated Ru(II) derivatives of 2-phenylpyridine (Hphpy) [Ru(phpy)(bpy)2]Cl (1a) and [Ru(phpy)(phen)2]Cl (1b) (bpy is 2,2'-bipyridine, phen is 1,10-phenanthroline) behave as noncompetitive inhibitors of glucose oxidase from Aspergillus niger in the enzyme-catalyzed oxidation of D-glucose by O2 into the corresponding lactone at pH 5.0 and 25 °C. The enzymatic activity has been measured by monitoring the O2 consumption. The inhibition constants K i are 0.036 and 0.017 M for 1a and 1b, respectively, indicating that 1b inhibits the enzymatic activity more efficiently than 1a. The well-known coordination compound [Ru(bpy)3]Cl2 (2) behaves, in contrast, as a competitive inhibitor, with K i = 0.018 M under the same conditions. The monophasic consumption of O2 in the case of 1a, 1b, and 2 is replaced by a distinct two-phase kinetics in the presence of the cyclometalated Ru(III) compound [Ru(phpy)(bpy)2]Cl2 (3), which was obtained from 1a in the presence of a large excess of H2O2 and the iron TAML activator. Interestingly, the rates of the first and the second phases are influenced by 3 in a different way. The rate of the first phase is noticeably higher in the presence of Ru(III), although the dependence is nonmonotonic and maximal acceleration is observed at the lowest loadings of 3. The rate of the second phase decreases monotonically on increasing the concentration of the ruthenium complex in solution. The nonmonotonic action of 3 was confirmed by using the doubly cyclometalated Ru(III) derivative [Ru(phpy)2(bpy)]Cl. The diverse rate variations induced by 3 accounted for acceleration by Ru(III) of the O2 reduction by the reduced form of glucose oxidase during the first phase, which ceases after the enzymatic reduction of Ru(III) to the Ru(II) species, the latter behaving similarly to 1a as the inhibitor of the enzyme.


Performance of MRS in metabolic profiling of the lumbar spinal cord in rat and mice.
In vivo magnetic resonance spectroscopy (MRS) of the rodent spinal cord (SC) is technically challenging. We investigated the feasibility of MRS in the SC of both rat and mice, by comparing the spectral characteristics. We assessed possible species dependent differences in the suitability for non-invasive metabolite monitoring in the SC. MR spectra using a STEAM sequence were acquired from a rectangular voxel in lumbar SC of rats and mice, after a two-step shim procedure. In addition to total choline (tCho) and total creatine (tCr), seven and eleven metabolites were reliably detected in rats and mice, respectively. No significant differences were observed in metabolite concentrations or spectral characteristics between species. Identification and quantification of major metabolites including the neurotransmitters γ-aminobutyric acid (GABA) and glycine (Gly) in the SC was successful in both rat and mice showing that investigation of SC neurochemical profiles is feasible in both species.


TET2, a tumor suppressor in hematological disorders.
The TET family of proteins has been described a few years ago. Only recently, their roles in DNA modification, through the oxidation of methyl-cytosine, and in normal and malignant development, through the description of TET2 as a tumor suppressor have been documented. The conjunction of these findings has prompted large efforts to understand the biology of these novel entities. Here, we summarize the recent results implicating TET2 in hematological malignancies suggesting that further studies are required to fully understand the role of DNA methylation alterations during transformation.


Intermittent trickling bed filter for the removal of methyl ethyl ketone and methyl isobutyl ketone.
Biodegradations of methyl ethyl ketone and methyl isobutyl ketone were performed in intermittent biotrickling filter beds (ITBF) operated at two different trickling periods: 12 h/day (ITBF-12) and 30 min/day (ITBF-0.5). Ralstonia sp. MG1 was able to degrade both ketones as evidenced by growth kinetic experiments. Results show that trickling period is an important parameter to achieve high removal performance and to maintain the robustness of Ralstonia sp. MG1. Overall, ITBF-12 outperformed ITBF-0.5 regardless of the target compound. ITBF-12 had high performance recovery at various inlet gas concentrations. The higher carbon dioxide production rates in ITBF-12 suggest higher microbial activity than in ITBF-0.5. Additionally, lower concentrations of absorbed volatile organic compound (VOC) in trickling solutions of ITBF-12 systems also indicate VOC removal through biodegradation. Pressure drop levels in ITBF-12 were relatively higher than in ITBF-0.5 systems, which can be attributed to the decrease in packed bed porosity as Ralstonia sp. MG1 grew well in ITBF-12. Nonetheless, the obtained pressure drop levels did not have any adverse effect on the performance of ITBF-12. Biokinetic constants were also obtained which indicated that ITBF-12 performed better than ITBF-0.5 and other conventional biotrickling filter systems.


Cytoprotective effect of novel histone deacetylase inhibitors against polyglutamine toxicity.
Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurological disorder caused by a CAG repeat expansion in the DRPLA gene encoding polyglutamine (polyQ). Although previous experimental studies have demonstrated that histone deacetylase (HDAC) inhibitors are therapeutically active, known HDAC inhibitors have considerable adverse effects clinically. To identify new HDAC inhibitors for the treatment of DRPLA, we evaluated a new series of HDAC inhibitors, N-hydroxycarboxamides, with our drug screening system, which uses neuronal PC12 cells stably transfected with a part of the DRPLA gene. We found that two of four N-hydroxycarboxamides significantly reduced polyQ-induced cell death. The essential structure of these compounds is a hydroxamic acid residue, which is shared with trichostatin A, a known HDAC inhibitor. Although our study showed mild neuroprotective effects, further structural modification of compounds that retain this residue may decrease cytotoxicity and increase protective activity against polyQ toxicity.


Humic acid-like material from sewage sludge stimulates culture growth of ectomycorrhizal fungi in vitro.
Significant effects of humic acid-like material (HALM) extracted from sewage sludge on dry matter production of cultures of ectomycorrhizal basidiomycetes were found in vitro. Mycelial growth of the majority of isolates tended to increase in the presence of the HALM and this effect was significant for 6 isolates. Strongest stimulation was observed in the case of Amanita muscaria, Leccinum aurantiacum and Lactarius deterrimus. The results suggest that the HALM can be used as an additive to media for cultivation of ectomycorrhizal basidiomycetes.


Individual and household factors associated with ownership of long-lasting insecticidal nets and malaria infection in south-central Ethiopia: a case-control study.
A recent considerable decline in malaria morbidity and mortality in Ethiopia is likely to be followed by changes in the practice of effective preventive measures and malaria risk factors. This study aimed to identify determinants of long-lasting insecticidal nets (LLINs) ownership and risk of malaria infection. A matched case-control study of 191 case and 377 control households was conducted between October 2014 and November 2015 in Adami Tullu district in south-central Ethiopia. Cases were microscopy or rapid diagnostic test confirmed malaria patients identified at three health centers and nine health posts, and matched on age with two neighbourhood controls. Information was collected on socio-demographic factors, house structure, knowledge on malaria and ownership of LLINs. The logistic regression model was used to determine predictors of LLINs ownership and malaria infection. All cases were infections due to either Plasmodium falciparum (71.2%) or Plasmodium vivax (28.8%). About 31% of the study households had at least one LLINs. Significant determinants of LLINs ownership were household's head malaria knowledge [adjusted odds ratio (AOR) = 2.47, 95% confidence interval (CI) 1.44-4.22], educational status [read and write (AOR = 6.88, 95% CI 2.30-20.55), primary education or higher (AOR = 5.40, 95% CI 1.57-18.55)], farmer respondent (AOR = 0.35, 95% CI 0.17-0.76), having ≥ 3 sleeping areas (AOR = 6.71, 95% CI 2.40-18.77) and corrugated roof type (AOR = 2.49, 95% CI 1.36-4.58). This study was unable to identify important risk factors of malaria infection with regard to sex, household wealth index, house structure, ownership of LLINs, keeping livestock inside house, staying overnight outdoor or having malaria during the last 6 months. Household socio-economic status, educational status and knowledge on malaria were important predictors of LLINs ownership. Households with farmer respondents were less likely to own LLINs. Addressing these factors could improve household's ownership of LLINs. The importance of factors associated with malaria infection was less evident in the current low transmission setting, and necessitates further epidemiological study.