Effect of human cell malignancy on activity of DNA polymerase iota.
An increased level of mutagenesis, partially caused by imbalanced activities of error prone DNA polymerases, is a key symptom of cell malignancy. To clarify the possible role of incorrect DNA polymerase iota (Pol iota) function in increased frequency of mutations in mammalian cells, the activity of this enzyme in extracts of cells of different mouse organs and human eye (melanoma) and eyelid (basal-cell skin carcinoma) tumor cells was studied. Both Mg2+, considered as the main activator of the enzyme reaction of in vivo DNA replication, and Mn2+, that activates homogeneous Pol iota preparations in experiments in vitro more efficiently compared to all other bivalent cations, were used as cofactors of the DNA polymerase reaction in these experiments. In the presence of Mg2+, the enzyme was active only in cell extracts of mouse testicles and brain, whereas in the presence of Mn2+ the activity of Pol iota was found in all studied normal mouse organs. It was found that in cell extracts of both types of malignant tumors (basal-cell carcinoma and melanoma) Pol iota activity was observed in the presence of either Mn2+ or Mg2+. Manganese ions activated Pol iota in both cases, though to a different extent. In the presence of Mn2+ the Pol iota activity in the basal-cell carcinoma exceeded 2.5-fold that in control cells (benign tumors from the same eyelid region). In extracts of melanoma cells in the presence of either cation, the level of the enzyme activity was approximately equal to that in extracts of cells of surrounding tumor-free tissues as well as in eyes removed after traumas. The distinctive feature of tissue malignancy (in basal-cell carcinoma and in melanoma) was the change in DNA synthesis revealed as Mn2+-activated continuation of DNA synthesis after incorrect incorporation of dG opposite dT in the template by Pol iota. Among cell extracts of different normal mouse organs, only those of testicles exhibited a similar feature. This similarity can be explained by cell division blocking that occurs in all normal cells except in testicles and in malignant cells.


Calcitriol but no other metabolite of vitamin D is essential for normal bone growth and development in the rat.
To determine the relative importance of different metabolites of vitamin D in bone growth and development, weanling male rat pups suckled by vitamin D-deficient mothers were given either calcitriol (1,25-dihydroxycholecalciferol) by continuous subcutaneous infusion, oral calcidiol (25-hydroxycholecalciferol), or oral 24,24-difluoro-25-hydroxycholecalciferol, a synthetic compound that can undergo 1-hydroxylation but not 24-hydroxylation, as their sole source of vitamin D for 40 d. Pups raised in the same manner, but given no vitamin D, served as controls. The three metabolites compared were given in doses that restored normal plasma calcium levels and normal increments in body weight. After in vivo double tetracycline labeling, bone histomorphometry by standard methods was performed on one femur and one tail vertebra. There were no significant differences between the three metabolite-treated groups in length, periosteal or endosteal diameter, cortical cross-sectional area, cortical porosity, osteoid thickness and volume, appositional rate and bone formation rate in the femur, or in qualitative and quantitative indices of endochondral ossification in the tail vertebra. All three groups differed markedly from the untreated controls with respect to all measurements. Collectively, the data indicate that neither calcidiol nor any 24-hydroxylated metabolite of calcidiol is needed in the rat (other than as a precursor) for longitudinal or transverse bone growth, for normal endochondral ossification, or for normal periosteal and endosteal formation, mineralization, and resorption of bone. Calcitriol was fully active with respect to each of the indices listed when given in a manner resembling its continuous endogenous production by the kidney, suggesting that previous reports of incomplete skeletal response to calcitriol result from its rapid clearance and infrequent oral administration. We demonstrated that calcitriol is the only metabolite that is both necessary and sufficient for normal bone growth and development in the rat, but our data do not indicate the extent to which its beneficial skeletal effects were mediated by direct action on bone, either of calcitriol itself or of some metabolite thereof, or by restoration of normal plasma levels of calcium and phosphate.


Reclassification of rhizosphere bacteria including strains causing corky root of lettuce and proposal of Rhizorhapis suberifaciens gen. nov., comb. nov., Sphingobium mellinum sp. nov., Sphingobium xanthum sp. nov. and Rhizorhabdus argentea gen. nov., sp. nov.
The genus Rhizorhapis gen. nov. (to replace the illegitimate genus name Rhizomonas) is proposed for strains of Gram-negative bacteria causing corky root of lettuce, a widespread and important lettuce disease worldwide. Only one species of the genus Rhizomonas was described, Rhizomonas suberifaciens, which was subsequently reclassified as Sphingomonas suberifaciens based on 16S rRNA gene sequences and the presence of sphingoglycolipid in the cell envelope. However, the genus Sphingomonas is so diverse that further reclassification was deemed necessary. Twenty new Rhizorhapis gen. nov.- and Sphingomonas-like isolates were obtained from lettuce or sow thistle roots, or from soil using lettuce seedlings as bait. These and previously reported isolates were characterized in a polyphasic study including 16S rRNA gene sequencing, DNA-DNA hybridization, DNA G+C content, whole-cell fatty acid composition, morphology, substrate oxidation, temperature and pH sensitivity, and pathogenicity to lettuce. The isolates causing lettuce corky root belonged to the genera Rhizorhapis gen. nov., Sphingobium, Sphingopyxis and Rhizorhabdus gen. nov. More specifically, we propose to reclassify Rhizomonas suberifaciens as Rhizorhapis suberifaciens gen. nov., comb. nov. (type strain, CA1(T) = LMG 17323(T) = ATCC 49355(T)), and also propose the novel species Sphingobium xanthum sp. nov., Sphingobium mellinum sp. nov. and Rhizorhabdus argentea gen. nov., sp. nov. with the type strains NL9(T) ( = LMG 12560(T) = ATCC 51296(T)), WI4(T) ( = LMG 11032(T) = ATCC 51292(T)) and SP1(T) ( = LMG 12581(T) = ATCC 51289(T)), respectively. Several strains isolated from lettuce roots belonged to the genus Sphingomonas, but none of them were pathogenic.


Is dietary fibre truly protective against colon cancer? A systematic review and meta-analysis.
Colorectal cancer is the third most common cancer worldwide. Growing evidence shows that about 47% of cases of colorectal cancer can be prevented by a healthy lifestyle. We performed a systematic review and meta-analysis aimed to evaluate the association between dietary fibre intake and the risk of colon cancer. We performed a structured computer search on PubMed, including epidemiological studies reporting results of dietary fibre intake and risk of colon cancer in women or men. We compared subjects exposed to the highest versus the lowest consumption. The search strategy identified 376 papers. After screening, 25 datasets were included in our meta-analysis. Results suggest a protective role of dietary fibre intake on colon cancer risk ES = 0.74 (95% CI = 0.67-0.82), p value = .000, but, moderate statistical heterogeneity (χ2 = 42.73, p value = .011) was found. Due to the high mortality of colorectal cancer, it is important to identify effective preventive measures, especially those of a healthy lifestyle, such as a healthy diet.


Mitogenic signalling pathway of tumour necrosis factor involves the rapid tyrosine phosphorylation of 41,000-Mr and 43,000-Mr cytosol proteins.
Tumour necrosis factor (TNF) is a potent mitogen for some fibroblast cell lines. Here we have examined the TNF-mediated changes in protein phosphorylation in Swiss 3T3 and human FS-4 fibroblasts, and compared them with changes observed after the treatment of cells with other mitogens, such as platelet-derived growth factor (PDGF) and bombesin. TNF stimulated the rapid phosphorylation of two 41,000-Mr and two 43,000-Mr cytosol proteins on tyrosine, threonine and/or serine, as did PDGF, epidermal growth factor and fibroblast growth factor; the increased levels of this mitogen-induced protein-tyrosine phosphorylation correlated well with the extent of mitogen-induced DNA synthesis as determined by the percentage of labelled nuclei. In contrast, bombesin, which is an even better mitogen for Swiss 3T3 cells than TNF, stimulated the tyrosine phosphorylation of 41,000-Mr and 43,000-Mr proteins only to a limited extent. On the other hand, bombesin and PDGF stimulated the rapid serine phosphorylation of an 80,000-Mr acidic protein, a major substrate for protein kinase C; increased phosphorylation of the 80,000-Mr protein was not observed at all when cells were stimulated with TNF. These results suggest significant differences among the mitogenic signalling pathways of TNF, PDGF and bombesin as regards the involvement of protein kinases; the mitogenic signalling pathway of TNF involves the activation of tyrosine kinase, but not of protein kinase C, whereas bombesin seems to transduce its mitogenic signal mainly through the activation of protein kinase C, and the activation of both kinases seems to be involved in the mitogenic signalling pathway of PDGF.


The multiscale coarse-graining method. XI. Accurate interactions based on the centers of charge of coarse-grained sites.
It is essential to be able to systematically construct coarse-grained (CG) models that can efficiently and accurately reproduce key properties of higher-resolution models such as all-atom. To fulfill this goal, a mapping operator is needed to transform the higher-resolution configuration to a CG configuration. Certain mapping operators, however, may lose information related to the underlying electrostatic properties. In this paper, a new mapping operator based on the centers of charge of CG sites is proposed to address this issue. Four example systems are chosen to demonstrate this concept. Within the multiscale coarse-graining framework, CG models that use this mapping operator are found to better reproduce the structural correlations of atomistic models. The present work also demonstrates the flexibility of the mapping operator and the robustness of the force matching method. For instance, important functional groups can be isolated and emphasized in the CG model.


Non-classical proIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent.
Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1.


Morphological characterization of the bursting and nonbursting neurones in the olfactory centre of the terrestrial slug limax marginatus
We investigated the morphological characteristics of physiologically characterized neurones in the procerebrum (PC) of the terrestrial slug Limax marginatus. The electrophysiological characteristics of the neurones were determined using the perforated patch recording technique. By comparing the shapes and sizes of somata, we found that the somata of bursting neurones were larger and had more oblong shapes than those of nonbursting neurones, indicating that the bursting and nonbursting neurones in the PC could be discriminated on the basis of the sizes and shapes of their soma. Injection of fluorescent dyes into the bursting and nonbursting neurones revealed morphological differences in the neurites. The bursting neurones had extensive projections within the cell body layer, and the major neurites of the bursting neurones were oriented along the dorsal-ventral axis. In contrast, the nonbursting neurones had neurites extending into the neuropile layers, where terminals of both sensory and presumed output neurones exist.


Polysaccharides from fermented Momordica charantia ameliorate obesity in high-fat induced obese rats.
Momordica charantia (M. charantia) has been widely used to treat obesity due to its bioactive ingredients. This research aimed to investigate the anti-obesity effect of polysaccharides (FP) from fermented M. charantia with Lactobacillus plantarum NCU116 on high-fat induced obese rats. We found that FP could effectively lower the body weight gain, Lee's index, insulin resistance and cell sizes of epididymal adipose tissues in obese rats compared with polysaccharides from non-fermented M. charantia (NFP). FP treatments decreased the total cholesterol, triacylglycerols, and low-density lipoprotein cholesterol, leptin, whereas they elevated the high-density lipoprotein cholesterol, adiponectin, significantly in the serum of obese rats. Furthermore, administrations of FP notably improved oxidative balance in obese rats. Lipidomics results indicated that 24 potential biomarkers have been identified in serum. Additionally, 21 lipids were considerably altered by FP and NFP intakes, such as fatty acyls, glycerolipids, sphingolipids, sterol lipids and glycerophospholipids. The anti-obesity properties of FP were revealed via relieving insulin resistance and fat accumulation of obese rats, which was associated with the regulation of lipid metabolism. Overall, FP exerted more favourable impacts on the anti-obesity effect than NFP, which may be attributed to fermentation.


Contextual Factors for Aging Well: Creating Socially Engaging Spaces Through the Use of Deliberative Dialogues.
Home and community engagement are key contextual factors for aging well, particularly for older adults in vulnerable social positions. A community-based participatory action research project conducted in Western Canada examined how to best use the shared amenity spaces in a low-income seniors' apartment complex in order to connect services and programs with tenants and to provide opportunities for service providers and local stakeholders to build upon and create new relationships toward collaboration and service delivery. Pre-move deliberative dialogue workshops (n = 4) were conducted with stakeholders (e.g., service providers, developers, and municipal government employees). Workshop participants (n = 24) generated ideas and plans on how physical and social environments can contribute to the social engagement of senior tenants. Shared dialogue led to community investment and asset sharing by integrating the knowledge and experiences of multiple stakeholder groups into the planning process. This article highlights how collaborative planning approaches for the effective use of the social environment (e.g., social programming), within the physical environment (e.g., amenity and community spaces), can generate rich and illuminating data for informing enhancements in the social environment of apartment dwelling low-income seniors. Contextual challenges to service provision are discussed, including the need for communication about and coordination of on-site programming, culturally diverse and responsive programming, and long-term funding. Prolonging independent community living with the assistance of support services should be a goal to both delay premature relocation into institutional care and meet the preferences of older adults.


The benefit of being a social butterfly: communal roosting deters predation.
Aposematic passion-vine butterflies from the genus Heliconius form communal roosts on a nightly basis. This behaviour has been hypothesized to be beneficial in terms of information sharing and/or anti-predator defence. To better understand the adaptive value of communal roosting, we tested these two hypotheses in field studies. The information-sharing hypothesis was addressed by examining following behaviour of butterflies departing from natural roosts. We found no evidence of roost mates following one another to resources, thus providing no support for this hypothesis. The anti-predator defence hypothesis was tested using avian-indiscriminable Heliconius erato models placed singly and in aggregations at field sites. A significantly higher number of predation attempts were observed on solitary models versus aggregations of models. This relationship between aggregation size and attack rate suggests that communally roosting butterflies enjoy the benefits of both overall decreased attack frequency as well as a prey dilution effect. Communal roosts probably deter predators through collective aposematism in which aggregations of conspicuous, unpalatable prey communicate a more effective repel signal to predators. On the basis of our results, we propose that predation by birds is a key selective pressure maintaining Heliconius communal roosting behaviour.


Mediators of the association between COVID-19-related stressors and parents' psychological flexibility and inflexibility: The roles of perceived sleep quality and energy.
The COVID-19 pandemic has forced parents across the United States to quickly transition to a new way of living. These transitions present new stressors, including the stress associated with physical health, with the demands of social distancing placed on families, and with the possibility of losing a job or not being able to pay bills. Such stressors have the potential to disrupt basic functioning, such as sleep and daily energy levels. Furthermore, the impact of stress might have repercussions on parents' capacities to be psychologically flexible, thus putting their psychological functioning at risk. Drawing upon a contextual behavioral science perspective, the current study sought to examine links between COVID-19-related stressors and psychological flexibility/inflexibility through such basic processes as parents' perceived sleep quality and daily energy level. A total of 1003 parents (97% from the US; 74% female; M = 40.9 years old, SD = 8.5) of children (ages 5-18) completed an online survey from the end of March to the end of April of 2020. Path analyses suggested that, after controlling health-related stress and the stress of work and parenting demands due to the pandemic directly predicting greater inflexibility and lower inflexibility, two mediation paths emerged. Specifically, higher levels of health-related stress were associated with lower levels of energy, which, in turn predicted lower levels of psychological flexibility. In addition, higher levels of health-related stress were associated with lower perceived sleep quality, which, in turn, was associated with higher levels of psychological inflexibility. In secondary analyses on the specific dimensions of flexibility and inflexibility, results suggested that lower energy levels indirectly linked health-related stress to lower levels of all 6 dimensions of flexibility and poorer sleep quality indirectly linked health-related stress to higher levels of self-as-content, fusion, and inaction. The stressors associated with COVID-19 pandemic have the potential to disrupt parents' perceived sleep quality and daily energy levels, reducing their abilities to respond to difficult or challenging experiences in a flexible manner and instead promoting more reactive and inflexible responses.


TiO2 nanotubes: synthesis and applications.
TiO(2) is one of the most studied compounds in materials science. Owing to some outstanding properties it is used for instance in photocatalysis, dye-sensitized solar cells, and biomedical devices. In 1999, first reports showed the feasibility to grow highly ordered arrays of TiO(2) nanotubes by a simple but optimized electrochemical anodization of a titanium metal sheet. This finding stimulated intense research activities that focused on growth, modification, properties, and applications of these one-dimensional nanostructures. This review attempts to cover all these aspects, including underlying principles and key functional features of TiO(2), in a comprehensive way and also indicates potential future directions of the field.


Trends, wealth inequalities and the role of the private sector in caesarean section in the Middle East and North Africa: A repeat cross-sectional analysis of population-based surveys.
To examine trends and variations of caesarean section by economic status and type of healthcare facility in Arab countries in the Middle East and North Africa (MENA). Secondary data analysis of nationally representative household surveys conducted between 2008-2020 across nine Arab countries in the MENA region. The study population was women aged 15-49 years with a live birth in the two years preceding the survey. Temporal changes in the proportion of deliveries by caesarean section in each country were calculated using generalised linear models and presented as risk differences (RD) with 95% confidence intervals (95%CI). Caesarean section was disaggregated by household wealth index and type of healthcare facility. Use of caesarean section ranged from 57.3% (95%CI:55.6-59.1%) in Egypt to 5.7% of births (95%CI:4.9-6.6%) in Yemen. Overall, the use of caesarean section has increased across the MENA region, except in Jordan, where there was no evidence of change (RD -2.3 (95%CI: -6.0 ‒1.4)). Across most countries, caesarean section use was highest in the richest quintile compared to the poorest quintile, for example, 42.8% (95%CI:38.0-47.6%) vs. 22.6% (95%CI:19.6-25.9%) in Iraq, respectively. Proportion of caesarean section was higher in private sector facilities compared to public sector: 21.8% (95%CI:18.2-25.9%) vs. 15.7% (95%CI:13.3-18.4%) in Yemen, respectively. Variations in caesarean section exist within and between Arab countries, and it was more commonly used amongst the richest quintiles and in private healthcare facilities. The private sector has a prominent role in observed trends. Urgent policies and interventions are required to address non-medically indicated intervention.


The Impact of Body Mass Index and Waist Circumference on Health-related Quality of Life Among Colorectal Cancer Survivors: Results from the PROFILES Registry.
We aimed to assess the association of waist circumference (WC) and body mass index (BMI) with health-related quality of life (HRQL) among colorectal cancer (CRC) survivors. CRC survivors diagnosed between 2000 and 2009 completed questionnaires in August 2013 (with self-reported weight, height, and self-assessed WC) and January 2014 (with HRQL using the EORTC-QLQ-C30). Clinical characteristics were retrieved from the Netherlands Cancer Registry. In multivariable linear regression analyses associations of BMI only, WC only and both BMI and WC with HRQL outcomes were assessed. 1,111 CRC survivors were included of whom 34% had a normal weight (18.5 ≤ BMI < 25 kg/m2), 49% had overweight (25 ≤ BMI < 30 kg/m2), 17% had obesity (BMI ≥ 30 kg/m2), and 44% had an increased WC (i.e., >102 and >88 cm for men and women, respectively). Both BMI and WC were separately associated with worse global health status, functioning, and more symptoms of fatigue. Increased WC was associated with lower physical, role and emotional functioning, regardless of BMI, with average differences ranging between 3 and 5 points. Future research on HRQL among CRC survivors should consider both BMI and WC. Furthermore, weight reduction trials should not only focus on general weight loss but also on the loss of abdominal fat.


Neuroimaging enrichment strategy for secondary prevention trials in Alzheimer disease.
We examined the improvement in statistical power that could be obtained in therapeutic trials for early (predementia) Alzheimer disease by constraining enrollment to individuals with amnestic mild cognitive impairment (MCI) and an atrophy pattern on a screening magnetic resonance imaging (MRI) scan previously found to be predictive of clinical decline, or to individuals with MCI and the apolipoprotein E epsilon 4 genetic risk factor for Alzheimer disease. Treatable effects were defined as absolute change versus change relative to healthy controls (HCs). Data from 168 HC and 299 MCI participants were analyzed to determine sample sizes required to detect 25% slowing in mean rate of decline using global function, cognitive function, and structural measures as outcome variables. Reductions in estimated sample sizes of 10% to 43% were observed using the genetic enrichment strategy; reductions of 43% to 60% were observed with the neuroimaging enrichment strategy. Sample sizes needed to detect slowing in rate of atrophy in MCI relative to HC were dramatically larger than those needed to detect absolute change in atrophy rates. Constraining enrollment to MCI subjects with predictive atrophy on a screening MRI scan could improve the efficiency of clinical trials. Failure to take into account normal age-related changes risks under-powering trials designed to test disease-modifying properties of potential treatments.


Pioglitazone improves ventricular diastolic function in patients with diabetes mellitus: a tissue Doppler study.
Pioglitazone treatment in type 2 diabetes mellitus produced significant improvements in glycaemic control, plasma lipids, blood pressure and inflammation. The aim of this study was to investigate the effect of pioglitazone on systolic and diastolic function in diabetic patients. Forty-nine diabetic patients were included in the study. The patients had never received thiazolidinedione therapy before. Clinical and echocardiographic variables were measured. 30 mg pioglitazone were administered. The patients were followed up for six months and all the measurements were re-evaluated for comparison. Body mass index (BMI) significantly increased after treatment. Fasting glucose, HbA1c and systolic blood pressure decreased. Insulin resistance improved and the HOMA-IR index decreased after pioglitazone treatment. Mean aortic diameter, left atrial systolic and diastolic volumes significantly decreased after therapy. Among diastolic function variables mitral E wave, E/A, ejection time and pulmonary vein peak reverse flow velocity (PVA) significantly increased whereas isovolumetric relaxation time (IVRT), isovolumetric contraction time (IVCT), deceleration time, E/E' and pulmonary vein late systolic flow (PVS2) decreased after pioglitazone therapy. Among tissue Doppler variables early (E) ventricular inflow velocities measured from the tricuspid lateral annulus, the mitral septal and lateral annulus, the anterior, inferior and posterior free wall significantly increased. Late (A) ventricular inflow velocities measured from the anterior, inferior free wall and the mitral septal annulus also increased. Pioglitazone treatment in type 2 diabetes mellitus produced significant improvements in measures of glycaemic control and diastolic ventricular function.


IL-22-STAT3 pathway plays a key role in the maintenance of ileal homeostasis in mice lacking secreted mucus barrier.
Muc2-deficient mice show no signs of ileal pathology but the mechanisms remained unknown. Wild-type (WT), Muc2, and Muc2 mice were killed at 2, 4, and 8 weeks of age. Total RNA from ileum was used for full genome transcriptome analysis and qPCR. Microbiota composition was determined using a mouse intestinal chip (MITChip). Morphological and immunohistological studies were performed on segments of ileum. The ileum was colonized by more diverse microbiota in young (week 4) WT than in Muc2 mice, and composition was influenced by genotype. Weaning was associated with major changes in the transcriptome of all mice, and the highest number of differentially expressed genes compared with adults, reflecting temporal changes in microbiota. Although the spatial compartmentalization of bacteria was compromised in Muc2 mice, gene set enrichment analysis revealed a downregulation of Toll-like receptor, immune, and chemokine signaling pathways compared to WT mice. The predicted effects of enhanced IL-22 signaling were identified in the Muc2 transcriptome as the upregulation of epithelial cell proliferation altered expression of mitosis and cell-cycle control pathways. This is consistent with increased villus length and number of Ki67 epithelial cells in Muc2 mice. Additionally, expression of the network of IL-22 regulated defense genes, including Fut2, Reg3β, Reg3γ, Relmb, and the Defensin Defb46 were increased in Muc2 mice. These findings highlight a role for the IL-22-STAT3 pathway in maintaining ileal homeostasis when the mucus barrier is compromised and its potential as a target for novel therapeutic strategies in inflammatory bowel disease.


Factor analysis of the Yale-Brown Obsessive Compulsive Scale in a family study of obsessive-compulsive disorder.
Our objective in this study was to determine whether symptoms of obsessive-compulsive disorder (OCD) cluster into groups that can usefully subclassify OCD. Psychiatrists or psychologists interviewed 221 subjects using the Lifetime Anxiety Version of the Schedule for Affective Disorders and Schizophrenia (SADS-LA) for the diagnosis of DSM-IV disorders, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for OCD symptoms. We analyzed 16 symptom categories from the Y-BOCS using exploratory factor analysis to identify latent symptom dimensions. The relationship between these symptom dimensions and clinical characteristics and familiality was investigated. A four-factor model emerged as the best classification of OCD symptoms in the Y-BOCS. These factors were labeled Pure Obsessions, Contamination, Symmetry/Order, and Hoarding. The contamination factor was least likely to be associated with other Axis I disorders. Whereas no significant relationship was found between the factor scores of probands and the presence of OCD in their first-degree relatives, the Symmetry/Order and Hoarding factors did breed true. Hoarding was found to predict poorer treatment response. A four-factor classification of OCD features best describes the symptom patterns of a sample of patients with OCD. There were specific clinical correlates for these factors, and significant intrafamilial sib-sib correlations were found for the Symmetry/Order and Hoarding factors.


The prevalence and management of central post-stroke pain at a hospital in Zimbabwe.
Central post-stroke pain (CPSP) is a poorly diagnosed chronic pain. It is under-treated and usually mismanaged. To establish the prevalence of CPSP and its management in stroke clinics at a tertiary hospital. This was a cross-sectional design with stroke patients and health professionals from the stroke clinic at the tertiary hospital in Zimbabwe. Out of 166 stroke survivors, 8% had CPSP. Younger age (<60 years) was significantly associated with CPSP (P<0.003). Pain characteristics of CPSP were hyperaesthesia (10, 71%), electric shocks (9, 64%), temperature allodynia (9, 64%) and allodynia (12, 86%). Ten health professionals participated in the study: one (10%) reported using Douleur Neuropathique 4 (to diagnose neuropathic pain) and two (20%) reported using sensory tests. Four patients (44%) were on paracetamol (acetaminophen) and on weak opiates such as codeine. None of the patients were on anticonvulsants or antidepressants. Two medical doctors (50%) used weak opiates as second-line management. Five patients (36%) reported receiving a combination of massage, stretching, general exercise and moist heat or cryotherapy. The prevalence of CPSP in the study group is within international range. There is a need for appropriate management and use of tests and outcome measures for diagnosis of CPSP.


Towards informed metrics for examining the role of human-induced animal responses in tag studies on wild animals.
Two prime issues can detrimentally affect animals that have been equipped with tags: (i) the effect of the capture and restraint process; and (ii) the effect of the tag itself. This work examines some of the issues surrounding quantification of tag effects on wild animals for both restrained and free-living animals. A new method to quantify stress effects based on monitoring ventilation rates in relation to activity is suggested for restrained animals which may help improve the practice of handling animals. It is also suggested that various metrics, many derived from accelerometers, can be examined in tagged wild animals to examine the change in behaviors over time with a view to having a better understanding of welfare issues, assuring the quality of recorded data and informing best practice.


[Relation between specific IgE antibodies to grass pollens and to wheat, rye, soya in children with allergic disease].
The aim of this study was to investigate the relationship between the hypersensitivity to grass pollens (gxl) and to wheat (f4), rye ff5) and soya (fl 4) in children with allergic disease. Specific IgE was determined by the FEIA CAP- System. Hypersensitivity was expressed in classes from 1 to 6. Specific IgE antibodies against grass (gxl) in 944 children with allergic disease, aged from 6 months to 18 years were detected. At the same time in 532 of these children - specific IgE to wheat and rye and in 122 children specific IgE to soya were also estimated. We detected very high correlation between the hypersensitivity to grass and the presence of specific IgE to wheat, rye (r=0.96, p<0.01) and soya (r=0.90, p<0.05).


Sex and Female Empowerment (SAFE): Learning from health care providers, men and women to design a sexual health intervention for women with substance use disorders.
Substance Use Disorder (SUD) treatment is a promising setting to provide sexual health education to women. This study examined barriers and possible solutions to effectively providing sexual health education and services during SUD treatment. To obtain a full picture of the barriers and solutions, 29 cisgender women and 17 cisgender men in treatment for a SUD and four health care providers in North Carolina were interviewed regarding the domains of pregnancy-planning, barriers to reproductive health services and contraception, selecting a method of contraception and desired aspects and elements of a sexual health intervention. Eight themes and 12 sub-themes emerged that included how addiction impacts pregnancy planning and pregnancy motivations, the stigma and fear regarding accessing health services, the lack of accurate knowledge of the human reproductive cycle and contraceptive methods and worries about contraception side-effects. Recommendations for interventions to reduce unintended pregnancy in this treatment population included the need for simple and focused information given by trusted communicators in a short time frame in accessible locations, and offering incentives for participation such as food and transportation. As SUD treatment providers and programs look to improve access to sexual health and contraceptive options for women with SUD, these eight themes provide helpful guidance in crafting future interventions.


Unique Epstein-Barr virus (EBV) latent gene expression, EBNA promoter usage and EBNA promoter methylation status in chronic active EBV infection.
Chronic active Epstein-Barr virus infection (CAEBV) has been considered to be a non-neoplastic T-cell lymphoproliferative disease associated with Epstein-Barr virus (EBV) infection. In EBV-associated diseases, the cell phenotype-dependent differences in EBV latent gene expression may reflect the strategy of the virus in relation to latent infection. We previously reported that EBV latent gene expression was restricted; EBV nuclear antigen 1 (EBNA1) transcripts were consistently detected in all spleen samples from five CAEBV patients, but EBNA2 transcripts were detected in only one sample. EBV latent gene expression is controlled by distinct usage of three EBNA promoters (Cp, Wp and Qp). In this study, we examined the EBNA promoter usage by RT-PCR and the methylation status in the Cp and Wp regions using bisulfite PCR analysis in spleen samples from CAEBV patients. EBNA1 transcripts were unexpectedly initiated not from Qp but from Cp in all samples in spite of the restricted form of latency. Furthermore, while Cp was active, Cp was heavily methylated, indicating that CAEBV has unique EBV latent gene expression, EBNA promoter usage and EBNA promoter methylation status, in part due to unique splicing of Cp-initiated transcripts and an activation mechanism in hypermethylated Cp.


Budding yeast 14-3-3 proteins contribute to the robustness of the DNA damage and spindle checkpoints.
Cells respond to DNA or mitotic spindle damage by activating specific pathways that halt the cell cycle to allow for possible repair. Here, we report that inactivation of one of the Saccharomyces cerevisiae 14-3-3 proteins, Bmh1, as well as the bmh1-S189P bmh2 mutant, failed to exhibit normal spindle damage-induced cell cycle delay and conferred hypersensitivity to benomyl or nocodazole. These defects were additive with those conferred by the bub2 and mad2 spindle checkpoint mutations. Following cdc13-1-induced DNA damage, the 14-3-3 response was additive with those provided by the Mec1 (ATR-related)-controlled Rad53 (CHK2-related) and Chk1 (CHK1-related) checkpoint pathways and also distinct from the PKA (Protein Kinase A)-controlled response. Therefore, the budding yeast 14-3-3 proteins contribute to the robustness of the two major mitotic checkpoints and, by doing so, may also ensure optimal coordination between the responses to two distinct types of damage.


Results, outcomes, and follow-up of remnants in the treatment of ophthalmic aneurysms: a 16-year experience of a combined neurosurgical and endovascular team.
Ophthalmic aneurysms present unique challenges to a vascular team. This study reviews the 16-year experience of a multidisciplinary neurovascular service in the treatment, complications, outcomes, and follow-up of patients with ophthalmic aneurysms from 1990 to 2005. A retrospective analysis of prospectively collected data of 134 patients with 157 ophthalmic aneurysms is presented. Subgroup analysis is performed based on treatment and clinical presentation of the patients. Clinical outcomes are reported using the Glasgow Outcome Scale. A "good" outcome is defined as a Glasgow Outcome Scale score of 4 or 5, and a "poor" outcome is defined as a Glasgow Outcome Scale score of 1 to 3. Outcome was related to patient age (P = 0.0002) and aneurysm size (P = 0.046). Outcomes for patients with ruptured aneurysms were related to hypertension (P < 0.0001) and clinical admission grade (P = 0.001). In patients with unruptured aneurysms, a good clinical outcome was noted in 103 (92.7%) of 111 patients at discharge and 83 (94.3%) of 88 patients at the time of the 1-year follow-up evaluation. Complete clipping was attained in 89 (79.5%) of 112 patients with angiographic follow-up. Patients with aneurysm remnants from both coiling and clipping had a low risk of regrowth, and there were no rehemorrhages. One of 25 patients with angiographic follow-up (average, 4.3 +/- 4.1 years) after "complete" clipping showed recurrence of the aneurysm. Despite the difficulties presented by ophthalmic aneurysms, these lesions can be successfully managed by a multidisciplinary team. Imaging follow-up of patients is important, as there is a risk of aneurysm regrowth after either coiling or clipping.


Combined antiretroviral therapy reduces brain viral load and pathological features of HIV encephalitis in a mouse model.
The role of brain HIV load in the pathogenesis of HIV-associated neurocognitive disorders (HAND) is unclear. To try and determine if the amount of HIV drives the severity of pathology, a severe combined immunodeficient (SCID) mouse model of HIV encephalitis (HIVE) was utilized to determine the effectiveness of a systemically administered combined antiretroviral (cART) regimen. SCID mice were inoculated intracerebrally with HIV-infected or uninfected (control) human macrophages and treated subcutaneously with cART or saline for 10 days. Immunohistochemistry was then used to examine gliosis and neuronal damage. Drug levels were measured in brain and plasma using high-performance liquid chromatography. Peak plasma and brain levels of atazanavir, tenofovir, and emtricitabine were determined to be 1 h post-injection of cART therapy. cART significantly reduced neuropathological features of HIVE, including astrogliosis and the presence of mononuclear phagocytes, and ameliorated reduced MAP2 (neuronal integrity) staining. However, cART did not eradicate HIV from the brain. Using this animal model of HIVE, these data indicate effective penetration of cART reduces brain viral loads and HIV pathology, possibly by eliminating the production of HIV proteins, virus infected cells, or both. Importantly, these data suggest that viral load directly affects the extent of pathology seen in the brain, particularly neuronal damage, which implies that more effective suppression of HIV in the CNS could reduce currently highly prevalent forms of HAND. However, these data also strongly suggest that cART will not eliminate HIV from the brain and that adjunctive therapies must be developed.


Routine abdominal drainage for uncomplicated laparoscopic cholecystectomy.
Laparoscopic cholecystectomy is the main method of treatment of symptomatic gallstones. Drains are used after laparoscopic cholecystectomy to prevent abdominal collections. However, drain use may increase infective complications and delay discharge. The aim is to assess the benefits and harms of routine abdominal drainage in uncomplicated laparoscopic cholecystectomy. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until March 2007. We included all randomised clinical trials comparing drainage with no drainage after laparoscopic cholecystectomy. Randomised clinical trials comparing one type of drain with another were also reviewed. We collected the data on the characteristics, methodological quality, mortality, abdominal collections, pain, nausea, vomiting, and hospital stay from each trial. We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis. For each outcome we calculated the odds ratio (OR) with 95% confidence intervals (CI) based on intention-to-treat analysis. We analysed five trials involving 591 patients randomised to drain (281) versus no drain (310). We also reviewed one trial with 41 patients randomised to suction drain (22) versus closed passive drain (19). The only trial that reported on abdominal collections requiring intervention reported no abdominal collections requiring intervention in either group. Wound infection tended to be higher in those with a drain (OR 15.38, 95% CI 0.86 to 275.74). Drainage was associated with lower shoulder, abdominal pain, and nausea, but this was not statistically significant. Hospital stay was longer in the drain group. Drain use after elective laparoscopic cholecystectomy reduces early post-operative pain, but increases wound infection rates and delays hospital discharge. We could not find evidence to support the use of drain after laparoscopic cholecystectomy.


Definition of murine T helper cell determinants in the major capsid protein of human papillomavirus type 16.
Three murine major histocompatibility complex (MHC) class II-restricted T cell determinants were identified in the major capsid protein L1 of human papillomavirus (HPV) type 16. Peptides derived from HPV-16 L1, which contain putative T cell epitopes located by a predictive algorithm, were synthesized and tested for lymphoproliferative activity by direct immunization, followed by in vitro assay of responses to peptides or recombinant HPV-16 L1. The MHC restriction of the stimulatory peptides was determined using blocking monoclonal antibodies against class II molecules. The responses, which were specific for the priming peptides alone, cross-reacted with recombinant L1 but not with analogous peptides derived from other HPV types.


The effect of tetracaine on stimulated contractions, sarcoplasmic reticulum Ca2+ content and membrane current in isolated rat ventricular myocytes.
1. The effects of tetracaine were examined on rat ventricular myocytes. In both field-stimulated and voltage-clamped cells tetracaine (100-200 microM) produced an initial decrease of contraction before a recovery towards the control level. Removal of tetracaine produced a transient overshoot of contraction to levels greater than the control. 2. The transient decrease of contraction produced by tetracaine was accompanied by a small transient increase in the integral of the L-type Ca2+ current and a larger transient decrease of the Na+-Ca2+ exchange current on repolarization. These are attributed to decreased systolic release of Ca2+. On removal of tetracaine there was an increase of the Na+-Ca2+ exchange current. Before the addition of tetracaine, calculated Ca2+ influx and efflux across the sarcolemma were approximately equal. On adding tetracaine, efflux was transiently less than influx and, on removal of tetracaine, efflux was greater than influx. 3. These changes in Ca2+ fluxes result in an increase of cell Ca2+ during exposure to tetracaine. The calculated magnitude of this increase was equal to that measured directly by applying caffeine (20 mM) to release sarcoplasmic reticulum (SR) Ca2+ and integrating the resulting Na+-Ca2+ exchange current. 4. It is concluded that the effects of tetracaine can be accounted for by depression of calcium-induced Ca2+ release (CICR). The response is transient because the inhibition is compensated for by an increase of SR Ca2+ content such that there is no steady-state effect on the magnitude of the systolic Ca2+ transient. The consequences of this result for the effects of other modulators of CICR are discussed.


Effect of Influenza Vaccination on the Reduction of the Incidence of Chronic Kidney Disease and Dialysis in Patients with Type 2 Diabetes Mellitus.
Patients with type 2 diabetes mellitus (T2DM) have a higher risk of chronic kidney disease (CKD) due to vascular complications and chronic inflammation. T2DM contributes to a higher risk of mortality and morbidity related to influenza. In Taiwan, influenza vaccination is recommended for patients with T2DM. A previous meta-analysis reported the efficacy of influenza vaccination in reducing hospitalization and mortality in patients with diabetes; however, the renal protective effect of the vaccine remains unclear. This study evaluated whether influenza vaccination could reduce the incidence of CKD and dialysis in patients with T2DM. The study cohort included all patients aged ≥55 years who were diagnosed as having T2DM between 1 January 2000 and 31 December 2012, by using data from Taiwan's National Health Insurance Research Database. Each patient was followed up with to assess factors associated with CKD. A time-dependent Cox proportional hazard regression model after adjustment for potential confounders was used to calculate the hazard ratio (HR) of CKD in the vaccinated and unvaccinated patients. The study population comprised 48,017 eligible patients with DM; 23,839 (49.7%) received influenza vaccination and the remaining 24,178 (50.3%) did not. The adjusted HRs (aHRs) for CKD/dialysis decreased in the vaccinated patients compared with the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs: 0.47/0.47, 0.48/0.49, and 0.48/0.48, respectively, all p < 0.0001). We observed similar protective effects against CKD during the influenza and noninfluenza seasons. Regardless of comorbidities or drug use, influenza vaccination was an independent protective factor. Furthermore, aHRs for CKD/dialysis were 0.71 (0.65−0.77)/0.77 (0.68−0.87), 0.57 (0.52−0.61)/0.69 (0.56−0.70), and 0.30 (0.28−0.33)/0.28 (0.24−0.31) in the patients who received 1, 2−3, and ≥4 vaccinations during the follow-up period, respectively. This population-based cohort study demonstrated that influenza vaccination exerts a dose-dependent and synergistic protective effect against CKD in the patients with T2DM with associated risk factors.


Midlife hypertension is a risk factor for some, but not all, domains of cognitive decline in later life: a systematic review and meta-analysis.
Management of midlife blood pressure and hypertension status may provide a window of intervention to mitigate cognitive decline with advancing age. The aim of this review was to investigate the relationship between midlife hypertension and cognition in midlife and later life. Online electronic databases were searched from their inception to May 2022. Studies assessing midlife (40-65 years) hypertension and cognition at mid and/or later-life were included. A random effects meta-analysis was deemed appropriate. One hundred forty-nine studies across 26 countries were included. Qualitative synthesis found negative relationships between midlife hypertension and later life cognition in the domains of memory, executive function, and global cognition. Metanalytical evidence revealed midlife hypertension negatively impacts memory, executive function, and global cognition but had no observed effect on attention at midlife. Hypertension at midlife has a significant negative impact on cognition in mid-life and later life, namely memory, executive function, and global cognition.


Radiographic follow-up of impacted third molars from age 20 to 32 years.
Nineteen patients (13 male, six female) with 34 impacted third molars, 21 in the mandible and 13 in the maxilla were radiographically followed from age 20 to 32. All were examined clinically and panoramic radiographs were taken at baseline and at the end of the study. Radiographic analysis included resorption of teeth, enlargement of the follicle, development of the root, change in inclination of the third molar, state of impaction, relative depth of the third molar in bone and relation to the ramus of the mandible and to the second molar tooth. In the mandible, the mean change in inclination was 19 degrees and the percentage of teeth with changed angulation was 76%. In the maxilla, only 23% of the teeth changed their inclination. The state of impaction (soft tissue, partially in bone, completely in bone) had changed for 44% of the teeth. According to the questionnaire, no pain or symptoms in the region of the third molars were reported by 74% of the students during the 12-year period. It is concluded that considerable radiographic changes, without notable symptoms, may occur involving inclination of the tooth and state of impaction in impacted third molars after the usual age of eruption.


[QTL analysis for epistatic effects and QTL x environment interaction effects on final height of rice (Oryza sativa L.)].
QTLs with epistatic effects and environmental interaction effects for final height of rice were studied by mixed-model based QTL mapping with a doubled haploid population from IR64/Azucena in four environments. The results demonstrated the importance of epistasis as a genetic basis of the quantitative traits and also revealed several important features of this phenomenon. In the results, 100 per cent of QTLs were involved in epistasis, of which 64 per cent were found with significant additive effects. This might mean that the usual estimates of the QTL additive effects could be confounded by epistatic interactions and result in biased estimation unless epistatic effect is separated. The other 36 per cent did not have any significant additive effects of their own but were involved in 48 per cent of the identified epistatic interactions. Such loci might play the role of modifying agents that tend to activate other loci or modify the action of other loci. The other features of epistasis include as follows: it was fairly common for the same locus to get involved in interactions with more than one locus; the QTLs with relatively high magnitude of effects might also be involved in epistasis; and epistasis was sensitive to environmental interactions for their expression. QTL x environment (QE) interaction effects were detected more often than QTL main effects for plant height behavior, as might indicate that gene expression could be greatly affected by environments.


Can technology and the media help reduce dysfunctional parenting and increase engagement with preventative parenting interventions?
In an evaluation of the television series "Driving Mum and Dad Mad," 723 families participated and were randomly assigned to either a standard or technology enhanced viewing condition (included additional Web-support). Parents in both conditions reported significant improvements from pre- to postintervention in their child's behavior, dysfunctional parenting, parental anger, depression, and self-efficacy. Short-term improvements were maintained at 6-months follow-up. Regressions identified predictors of program outcomes and level of involvement. Parents who watched the entire series had more severe problems at preintervention and high sociodemographic risk than parents who did not watch the entire series. Few sociodemographic, child, or parent variables assessed at preintervention predicted program outcomes or program engagement, suggesting that a wide range of parents from diverse socioeconomic status benefited from the program. Media interventions depicting evidence-based parenting programs may be a useful means of reaching hard to engage families in population-level child maltreatment prevention programs.


An open-data-driven agent-based model to simulate infectious disease outbreaks.
Agent-based models are a tool that can be used to better understand the dynamics of an infectious disease outbreak. An infectious disease outbreak is influenced by many factors including vaccination or immunity levels, population density, and the age structure of the population. We hypothesize that these factors along with interactions of factors and the actions of individuals would lead to outbreaks of different size and severity even in two towns that appear similar on paper. Thus, it is necessary to implement a model that is able to capture these interactions and the actions of individuals. Using openly available data we create a data-driven agent-based model to simulate the spread of an airborne infectious disease in an Irish town. Agent-based models have been known to produce results that include the emergence of patterns and behaviours that are not directly programmed into the model. Our model is tested by simulating an outbreak of measles that occurred in Schull, Ireland in 2012. We simulate the same outbreak in 33 different towns and look at the correlations between the model results and the town characteristics (population, area, vaccination rates, age structure) to determine if the results of the model are affected by interactions of those town characteristics and the decisions on the agents in the model. As expected our results show that the outbreaks are not strongly correlated with any of the main characteristics of the towns and thus the model is most likely capturing such interactions and the agent-based model is successful in capturing the differences in the outbreaks.


Potential biomarkers of exposure and effect among glass craftsmen and braziers exposed to nitrogen oxides.
The purpose of this research was to determine occupational exposure of glass craftsmen and braziers to inhaled nitrogen oxides nitrogen dioxide and nitric oxide and to relate this to urinary nitrate, hydroxyproline and thioethers and to breath pentane. The glass craftsmen were exposed to nitrogen oxides at levels exceeding the occupational exposure standard and higher than braziers or controls. Urinary nitrate excretion was elevated. In these exposed workers hydroxyproline, thioethers and breath pentane were all elevated compared with controls and higher than in braziers who were less exposed. There was, however, only a correlation between individual levels of exposure nitrogen oxides in the breathing zone and breath pentane and there were no individual correlations between markers of effect and excretion of nitrate in the urine at the sample time.


Environmental changes in the North Atlantic Region: SCANNET as a collaborative approach for documenting, understanding and predicting changes.
The lands surrounding the North Atlantic Region (the SCANNET Region) cover a wide range of climate regimes, physical environments and availability of natural resources. Except in the extreme North, they have supported human populations and various cultures since at least the end of the last ice age. However, the region is also important at a wider geographical scale in that it influences the global climate and supports animals that migrate between the Arctic and all the other continents of the world. Climate, environment and land use in the region are changing rapidly and projections suggest that global warming will be amplified there while increasing land use might dramatically reduce the remaining wilderness areas. Because much of the region is sparsely populated--if populated at all--observational records of past environmental changes and their impacts are both few and of short duration. However, it is becoming very important to record the changes that are now in progress, to understand the drivers of these changes, and to predict future consequences of the changes. To facilitate research into understanding impacts of global change on the lands of the North Atlantic Regions, and also to monitor changes in real time, an EU-funded network of research sites and infrastructures was formed in 2000: this was called SCANNET--SCANdinavian/North European NETwork of Terrestrial Field Bases. SCANNET currently consists of 9 core sites and 5 sites within local networks that together cover the broad range of current climate and predicted change in the region. Climate observations are well replicated across the network, whereas each site has tended to select particular environmental and ecological subjects for intensive observation. This provides diversity of both subject coverage and expertise. In this paper, we summarize the findings of SCANNET to-date and outline its information bases in order to increase awareness of data on environmental change in the North Atlantic Region. We also identify important gaps in our understanding and identify where the roles of existing infrastructures and activities represented by SCANNET can facilitate future research, monitoring and ground-truthing activities.


Role of environmental poliovirus surveillance in global polio eradication and beyond.
Environmental poliovirus surveillance (ENV) means monitoring of poliovirus (PV) transmission in human populations by examining environmental specimens supposedly contaminated by human faeces. The rationale is based on the fact that PV-infected individuals, whether presenting with disease symptoms or not, shed large amounts of PV in the faeces for several weeks. As the morbidity:infection ratio of PV infection is very low, this fact contributes to the sensitivity of ENV which under optimal conditions can be better than that of the standard acute flaccid paralysis (AFP) surveillance. The World Health Organization has included ENV in the new Strategic Plan of the Global Polio Eradication Initiative for years 2010-2012 to be increasingly used in PV surveillance, supplementing AFP surveillance. In this paper we review the feasibility of using ENV to monitor wild PV and vaccine-derived PV circulation in human populations, based on global experiences in defined epidemiological situations.


Heterochromatin staining pattern of quail-chicken hybrid lymphocytes.
Feulgen-Rossenbeck staining of lymphoid cells of quail-chicken hybrids in histologic sections revealed a pattern of heterochromatin arrangement distinguishable from that of either parental type. During interphase, hybrid lymphocytes exhibited combined characteristics of both the parental quail and the parental chicken. Hybrid heterochromatin was arranged in a large central mass as in the quail and in fairly evenly distributed small chromacenters around the periphery of the nucleus similar to the arrangement in the chicken. It is suggested that this pattern of staining can be used as a marker for hybrid cells in studies of genetic interactions.


Active Haptic Exploration of Softness: Indentation Force Is Systematically Related to Prediction, Sensation and Motivation.
Active finger movements play a crucial role in natural haptic perception. For the perception of different haptic properties people use different well-chosen movement schemes (Lederman and Klatzky, 1987). The haptic property of softness is stereotypically judged by repeatedly pressing one's finger against an objects' surface, actively indenting the object. It has been shown that people adjust the peak indentation forces of their pressing movements to the expected stimulus' softness in order to improve perception (Kaim and Drewing, 2011). Here, we aim to clarify the mechanisms underlying such adjustments. We disentangle how people modulate executed peak indentation forces depending on predictive vs. sensory signals to softness, and investigate the influence of the participants' motivational state on movement adjustments. In Experiment 1, participants performed a two alternative forced-choice (2AFC) softness discrimination task for stimulus pairs from one of four softness categories. We manipulated the predictability of the softness category. Either all stimuli of the same category were presented in a blocked fashion, which allowed predicting the softness category of the upcoming pair (predictive signals high), or stimuli from different categories were randomly intermixed, which made prediction impossible (predictive signals low). Sensory signals to softness category of the two stimuli in a pair are gathered during exploration. We contrasted the first indentation (sensory signals low) and last indentation (sensory signals high) in order to examine the effect of sensory signals. The results demonstrate that participants systematically apply lower forces when softer objects (as compared to harder objects) are indicated by predictive signals. Notably, sensory signals seemed to be not as relevant as predictive signals. However, in Experiment 2, we manipulated participant motivation by introducing rewards for good performance, and showed that the use of sensory information for movement adjustments can be fostered by high motivation. Overall, the present study demonstrates that exploratory movements are adjusted to the actual perceptual situation and that in the process of fine-tuning, closed- and open-loop mechanisms interact, with varying contributions depending on the observer's motivation.


Novel Aspergillus hemicellulases enhance performance of commercial cellulases in lignocellulose hydrolysis.
A novel hemicellulase-producing fungal strain was isolated from a local soil sample. The organism is identified as Aspergillus fumigatus based on ribosomal RNA analyses. The Aspergillus strain, designated as 2NB, produces both enzymes acting on xylan backbone (xylanase and β-xylosidase), and those acting on side chains (or accessory enzymes) notably α-arabinofuranosidase and acetyl-xylan esterase. The Asperigillus hemicellulases are characterized as having relatively low xylanase and β-xylosidase activities but high side chain removal activities. The activity ratio of side-chain acting enzymes to xylanase is higher than that of the Multifect enzyme, a commercial hemicellulase product. The potential of the novel hemicellulases in lignocelluloses bioprocessing was demonstrated with alkaline-pretreated switchgrass as lignocellulose substrate with hemicellulase supplemented with a ratio of xylanase activity to filter paper unit of 2:1. Supplement of Aspergillus hemicellulases to commercial cellulases significantly enhanced the hydrolysis of lignocellulose, achieving a 94% hydrolysis yield based on reducing sugar measurement, compared to 60% when no hemicellulase or 75% when Multifect enzyme was used under otherwise identical conditions. The significant improvement resulting from supplementing a hemicellulase mix with high side-chain removal activities suggests the importance of accessory hemicellulases in lignocellulose processing.


A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability.
The ability to regulate DNA replication initiation in response to changing nutrient conditions is an important feature of most cell types. In bacteria, DNA replication is triggered by the initiator protein DnaA, which has long been suggested to respond to nutritional changes; nevertheless, the underlying mechanisms remain poorly understood. Here, we report a novel mechanism that adjusts DnaA synthesis in response to nutrient availability in Caulobacter crescentus. By performing a detailed biochemical and genetic analysis of the dnaA mRNA, we identified a sequence downstream of the dnaA start codon that inhibits DnaA translation elongation upon carbon exhaustion. Our data show that the corresponding peptide sequence, but not the mRNA secondary structure or the codon choice, is critical for this response, suggesting that specific amino acids in the growing DnaA nascent chain tune translational efficiency. Our study provides new insights into DnaA regulation and highlights the importance of translation elongation as a regulatory target. We propose that translation regulation by nascent chain sequences, like the one described, might constitute a general strategy for modulating the synthesis rate of specific proteins under changing conditions.


New evidence in severe pneumonia: imipenem/ cilastatin/relebactam.
Imipenem combined with beta-lactamase inhibitor relebactam (IMI/REL) has an extensive bactericidal activity against Gram-negative pathogens producing class A or class C beta-lactamases, not active against class B and class D. The phase 3 clinical trial (RESTORE-IMI-2), double-blind, randomized, evaluated IMI/REL vs. piperacillin-tazobactam (PIP/TAZ) for treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), demonstrated non-inferiority at all-cause mortality at 28 days (15.9% vs 21.3%), favorable clinical response at 7-14 days end of treatment (61% vs 59.8%) and with minor serious adverse effects (26.7% vs 32%). IMI/REL is a therapeutic option in HAP and VAP at approved dosage imipenem 500 mg, cilastatin 500 mg and relebactam 250 mg once every 6h, by an IV infusion over 30 min.


Cigarette smoke exposure alters [14C]arachidonic acid metabolism in aortas and platelets of rats fed various levels of selenium and vitamin E.
Rats were placed on a basal diet supplemented with 0, 0.03, or 3 ppm selenium and 0 or 20 ppm vitamin E for 41-43 wk. Selenium deficiency decreased hepatic glutathione peroxidase activity and lowered both aortic prostacyclin (PGI2) and platelet thromboxane (TXA2) production compared to selenium- and vitamin E-supplemented animals. Vitamin E deficiency increased hepatic lipid peroxidation and decreased aortic PGI2 synthesis. Rats exposed daily for 31-32 wk to fresh smoke from a UK 2R1 reference cigarette had carboxyhemoglobin levels of 0.75 +/- 0.12 and 4.73 +/- 0.12% in sham- and smoke-exposed groups, respectively. Animals chronically exposed to cigarette smoke displayed a nearly twofold increase in pulmonary arylhydrocarbon hydroxylase activity. Smoke exposure produced a 26-33% decrease in aortic PGI2 synthesis compared to shams in the Se3E20, Se0.03E20, and Se3E0 groups. Smoking also increased platelet thromboxane 91% and 98% in the Se3E20 and Se3E0 groups compared to shams. It is concluded that cigarette-smoke exposure and selenium or vitamin E deficiency alter aortic PGI2 and platelet TXA2 production.


ComplexViewer: visualization of curated macromolecular complexes.
Proteins frequently function as parts of complexes, assemblages of multiple proteins and other biomolecules, yet network visualizations usually only show proteins as parts of binary interactions. ComplexViewer visualizes interactions with more than two participants and thereby avoids the need to first expand these into multiple binary interactions. Furthermore, if binding regions between molecules are known then these can be displayed in the context of the larger complex. freely available under Apache version 2 license; EMBL-EBI Complex Portal: http://www.ebi.ac.uk/complexportal; Source code: https://github.com/MICommunity/ComplexViewer; Package: https://www.npmjs.com/package/complexviewer; http://biojs.io/d/complexviewer. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js. firstname.lastname@example.com or firstname.lastname@example.com.


Prediction on the seasonal behavior of hydrogen sulfide using a neural network model.
Models to predict seasonal hydrogen sulfide (H2S) concentrations were constructed using neural networks. To this end, two types of generalized regression neural networks and radial basis function networks are considered and optimized. The input data for H2S were collected from August 2005 to Fall 2006 from a huge industrial complex located in Ansan City, Korea. Three types of seasonal groupings were prepared and one optimized model is built for each dataset. These optimized models were then used for the analysis of the sensitivity and main effect of the parameters. H2S was noted to be very sensitive to rainfall during the spring and summer. In the autumn, its sensitivity showed a strong dependency on wind speed and pressure. Pressure was identified as the most influential parameter during the spring and summer. In the autumn, relative humidity overwhelmingly affected H2S. It was noted that H2S maintained an inverse relationship with a number of parameters (e.g., radiation, wind speed, or dew-point temperature). In contrast, it exhibited a declining trend with a decrease in pressure. An increase in radiation was likely to decrease during spring and summer, but the opposite trend was predicted for the autumn. The overall results of this study thus suggest that the behavior of H2S can be accounted for by a diverse combination of meteorological parameters across seasons.


Intranasal interleukin-12 treatment promotes antimicrobial clearance and survival in pulmonary Francisella tularensis subsp. novicida infection.
Francisella tularensis is a highly virulent facultative intracellular bacterium and is considered a potential biological warfare agent. Inhalation tularemia can lead to the development of bronchopneumonia, which is frequently fatal without medical intervention. Treatment strategies that directly target the respiratory mucosa may extend the efficacy of therapy, particularly for the medical management of acute aerosol exposure. To this end, we describe an intranasal (i.n.) strategy for the treatment of pulmonary Francisella infection in mice that uses a combinatorial approach with the conventional antibiotic gentamicin and interleukin 12 (IL-12). The i.n. administration of IL-12 alone promoted bacterial clearance and extended the time to death but did not prevent mortality against lethal pulmonary challenge with Francisella tularensis subsp. novicida. However, i.n. treatment with gentamicin and IL-12 therapeutically at 8 and 24 h after challenge markedly enhanced the rate of survival (70 to 100%) against pulmonary infection compared to the rates of survival for animals treated with antibiotic alone (17%) or IL-12 alone (0%). A delay in combinatorial therapy over a span of 4 days progressively decreased the efficacy of this treatment regimen. This combinatorial treatment was shown to be highly dependent upon the induction of endogenous gamma interferon and may also involve the activation of natural killer cells. Together, these findings suggest that IL-12 may be a potent adjunct for chemotherapy to enhance drug effectiveness against pulmonary Francisella infection.


Will swine veterinarians lead by meeting the next-generation needs of our industry?
The US swine industry is currently challenged by the potential of transboundary animal disease (eg, African swine fever) entry to the national herd and the relentless pressures of domestic diseases (eg, porcine reproductive and respiratory syndrome). The task of the swine veterinarian is to biosecure both the national herd and their customers' local farms to mitigate these risks. This Viewpoint raises 4 questions that swine veterinarians, including practicing (private and corporate), industry, research, academic, and regulatory (state and federal) veterinarians who spend a portion of their time controlling, treating, preventing, or eradicating diseases of swine, must answer to meet the needs of their farms to compete globally and survive. In addition, it appears that there is sufficient science-based information to move forward in a collaborative manner and that the goals of prevention of African swine fever and elimination of porcine reproductive and respiratory syndrome virus are technically possible. Therefore, as previous generations of swine veterinarians led the US industry in the elimination of foot-and-mouth disease virus, classical swine fever virus, and pseudorabies virus from the national herd, the central challenge is whether the next generation of veterinarians will provide the necessary leadership to deal with the current industry and its next-generation challenges.


Simple spectrophotometric methods for estimation of aceclofenac from bulk and formulations.
Two simple, precise and accurate visible spectrophotometric methods were developed for the estimation of Aceclofenac in bulk drug and in pharmaceutical formulations. The proposed methods were indirect and based on determination of aceclofenac after its reaction with either (p-dimethylaminocinnamaldehyde or 3-Methyl-2-benzothiazolinone hydrazine hydrochloride and measuring the chromogen at the λmax by 658 and 592, respectively. Beers law obeyed in the concentration range of 1-200 μg/ml for method A and 1-100 μg/ml for method B. The accuracy of the methods was determined by recovery studies. The methods showed good reproducibility and recovery with relative standard deviation (in %) less than 2. The methods were found to be simple, economical, accurate and reproducible and can be used for routine analysis of Aceclofenac in bulk drug and in pharmaceutical formulations.


Cs(2)UPd(3)Se(6).
Dicaesium uranium(IV) tripalladium(II) hexa-selenide, Cs(2)UPd(3)Se(6), crystallizes in the space group Fmmm in the Ba(2)NaCu(3)O(6) structure type. The asymmetric unit comprises the following atoms with site symmetries as shown: U1 (mm2), Cs1 (222), Cs2 (m2m), Pd1 (.m.), Pd2 (2mm), Se1 (m..), and Se2 (1). This layered structure contains six edge-sharing square-planar [PdSe(4)] units that form a hexa-gon. These, in turn, edge-share with [USe(6)] trigonal-prismatic units, forming an extended layer parallel to (010). The layers are stacked along [010]. They are staggered, and are separated by the Cs atoms. The Cs atoms are either coordinated in a square anti-prism of Se atoms or are ten-coordinate, with one square face and the opposite face hexa-gonal.


Conversion of retinol to retinal by rat liver microsomes.
An NADPH-requiring enzyme present in rat liver microsomes catalyzes the conversion of retinol to retinal; the enzyme activity is induced by 3-methylcholanthrene (MC). The optimum activities for both the constitutive and induced reactions occur within a pH range of 8.2-8.7. For the constitutive enzyme, the KM and Vmax values are 285 microM retinol and 18 nmol of retinal/mg protein/hr, respectively; for the MC-induced activity, the corresponding values are 133 microM retinol and 33 nmol of retinal/mg protein/hr. Neither the constitutive nor the induced activities are detectable in microsomes from seven other tissues. Both hepatic activities are inhibited by citral, ketoconazole, SKF 525-A, and alpha-naphthoflavone; both are stimulated by divalent cations. Neither is inhibited by 3-amino-1,2,4-triazole, pyrazole, or sodium azide or stimulated by monovalent cations. The enzyme appears to be a previously unreported retinol oxidase, distinct from the known cytosolic enzymes, retinal reductase and retinol dehydrogenase.


Unsupervised Clustering Analysis Based on MODS Severity Identifies Four Distinct Organ Dysfunction Patterns in Severely Injured Blunt Trauma Patients.
Purpose: We sought to identify a MODS score parameter that highly correlates with adverse outcomes and then use this parameter to test the hypothesis that multiple severity-based MODS clusters could be identified after blunt trauma. Methods: MOD score across days (D) 2-5 was subjected to Fuzzy C-means Clustering Analysis (FCM) followed by eight Clustering Validity Indices (CVI) to derive organ dysfunction patterns among 376 blunt trauma patients admitted to the intensive care unit (ICU) who survived to discharge. Thirty-one inflammation biomarkers were assayed (Luminex™) in serial blood samples (3 samples within the first 24 h and then daily up to D 5) and were analyzed using Two-Way ANOVA and Dynamic Network analysis (DyNA). Results: The FCM followed by CVI suggested four distinct clusters based on MOD score magnitude between D2 and D5. Distinct patterns of organ dysfunction emerged in each of the four clusters and exhibited statistically significant differences with regards to in-hospital outcomes. Interleukin (IL)-6, MCP-1, IL-10, IL-8, IP-10, sST2, and MIG were elevated differentially over time across the four clusters. DyNA identified remarkable differences in inflammatory network interconnectivity. Conclusion: These results suggest the existence of four distinct organ failure patterns based on MOD score magnitude in blunt trauma patients admitted to the ICU who survive to discharge.


Effect of B cell stimulatory factor-1 (interleukin 4) on Fc epsilon and Fc gamma receptor expression on murine B lymphocytes and B cell lines.
Culture of murine splenic B cells with interleukin 4 (IL-4) caused the up-regulation of the lymphocyte Fc receptor for immunoglobulin E (IgE) (Fc epsilon R) over a similar dose range as required for Ia up-regulation. However, the expression level of the Fc receptor for immunoglobulin G (Fc gamma R) did not increase, rather IL-4 caused a slight but consistent decrease in the Fc gamma R level on the B cells. Fc epsilon R+ B hybridoma cells also responded to IL-4 by exhibiting increased Fc epsilon R expression; with the hybridoma cells Fc gamma R levels were unaffected. IL-4 caused an increase in the number of Fc epsilon R per cell and the highest levels of expression were obtained by having both IgE and IL-4 present in the culture. The specificity of the increase was demonstrated by blocking IL-4-mediated actions with monoclonal anti-IL-4 (11B11). Experiments following the incorporation of [35S]methionine into the Fc epsilon R demonstrated that IL-4 increased the rate of Fc epsilon R biosynthesis; this provides an explanation for the IL-4-induced increase in Fc epsilon R expression. IL-4, unlike IgE, had no effect on the rate of degradation of the Fc epsilon R. Interferon-gamma (IFN-gamma) totally abrogated IL-4-mediated Fc epsilon R up-regulation; at the same concentration of IFN-gamma Ia up-regulation is also suppressed, although not as effectively. IFN-gamma was shown to directly suppress Fc epsilon R synthesis, thereby explaining the inhibitory action on Fc epsilon R levels. Finally, it was shown that 11B11 inhibited the increased expression of Fc epsilon R on B cells obtained from mice during the early, but not the late, stages of Nippostrongylus brasiliensis infection. This latter finding suggests that the high Fc epsilon R levels seen early in parasite infections are dependent upon IL-4. The results overall provide further insight into the biologic activities of IL-4.


A method for estimating the orientation of a directional sound source from source directivity and multi-microphone recordings: principles and application.
Taking into account directivity of real sound sources makes it possible to try solving an interesting and biologically relevant problem: estimating the orientation in three-dimensional space of a directional sound source. The source, of known directivity, produces a broadband signal (in the ultrasonic range, in this application) that is recorded by microphones whose position with respect to source is known. An analytical method to process the recorded signals and estimate source orientation is developed in this paper. Experiments testing method performance in estimating source orientation were performed both in a laboratory environment with a Polaroid transducer as source and in a flight room with a Myotis daubentonii bat. In the first case, results showed the estimation method to be accurate and pointed out its limitations. The latter case is significant as an example biological application of the method for extracting behavioral features from bats; results are compared with alternative calculations based on microphone root-mean-square (rms)-pressure values.


[C-Reactive protein and SOFA scale: A simple score as early predictor of critical care requirement in patients with COVID-19 pneumonia in Spain].
To identify potential markers at admission predicting the need for critical care in patients with COVID-19 pneumonia. An approved, observational, retrospective study was conducted between March 15 to April 15, 2020. 150 adult patients aged less than 75 with Charlson comorbidity index ≤ 6 diagnosed with COVID-19 pneumonia were included. Seventy-five patients were randomly selected from those admitted to the critical care units (critical care group [CG]) and seventy-five hospitalized patients who did not require critical care (non-critical care group [nCG]) represent the control group. One additional cohort of hospitalized patients with COVID-19 were used to validate the score. Multivariable regression showed increasing odds of in-hospital critical care associated with increased C-reactive protein (CRP) (odds ratio 1.052 [1.009-1.101]; P = .0043) and higher Sequential Organ Failure Assessment (SOFA) score (1.968 [1.389-2.590]; P < .0001), both at the time of hospital admission. The AUC-ROC for the combined model was 0.83 (0.76-0.90) (vs AUC-ROC SOFA P < .05). The AUC-ROC for the validation cohort was 0.89 (0.82-0.95) (P > 0.05 vs AUC-ROC development). Patients COVID-19 presenting at admission SOFA score ≥ 2 combined with CRP ≥ 9,1 mg/mL could be at high risk to require critical care.


Hemangiosarcoma in the cat: retrospective evaluation of 31 surgical cases.
Hemangiosarcoma was diagnosed in 31 cats. Diagnosis was confirmed by surgical biopsy. Locations of the primary tumors were the abdominal cavity (15 cats), sc tissue (13 cats), thoracic cavity (2 cats), and nasal cavity (1 cat). Nine (60%) of the 15 cats with abdominal hemangiosarcoma had extrathoracic evidence of metastasis: this was not found in the other cats. Of the cats with tumors located in the sc tissue, 6 of 10 (60%) evaluated on a long-term basis had local recurrence of the tumor. Eleven cats were not available for follow-up evaluation, 3 cats were euthanatized at the time of surgery, and 2 others were euthanatized within the first postoperative week subsequent to histologic diagnosis of hemangiosarcoma. Of the remaining 15 cats, 4 with abdominal hemangiosarcoma and 5 with hemangiosarcoma of the sc tissue died at means of 22 and 44 weeks, respectively.


Floral organ abscission peptide IDA and its HAE/HSL2 receptors control cell separation during lateral root emergence.
Throughout their life cycle, plants produce new organs, such as leaves, flowers, and lateral roots. Organs that have served their purpose may be shed after breakdown of primary cell walls between adjacent cell files at the site of detachment. In Arabidopsis, floral organs abscise after pollination, and this cell separation event is controlled by the peptide INFLORESCENCE DEFICIENT IN ABSCISSION (IDA), which signals through the leucine-rich repeat receptor-like kinases HAESA (HAE) and HAESA-LIKE2 (HSL2). Emergence of new lateral root primordia, initiated deep inside the root under the influence of auxin, is similarly dependent on cell wall dissolution between cells in the overlaying endodermal, cortical, and epidermal tissues. Here we show that this process requires IDA, HAE, and HSL2. Mutation in these genes constrains the passage of the growing lateral root primordia through the overlaying layers, resulting in altered shapes of the lateral root primordia and of the overlaying cells. The HAE and HSL2 receptors are redundant in function during floral organ abscission, but during lateral root emergence they are differentially involved in regulating cell wall remodeling genes. In the root, IDA is strongly auxin-inducible and dependent on key regulators of lateral root emergence--the auxin influx carrier LIKE AUX1-3 and AUXIN RESPONSE FACTOR7. The expression levels of the receptor genes are only transiently induced by auxin, suggesting they are limiting factors for cell separation. We conclude that elements of the same cell separation signaling module have been adapted to function in different developmental programs.


In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin's lymphoma (NHL).
The analysis of cellular networks and pathways involved in oncogenesis has increased our knowledge about the pathogenic mechanisms that underlie tumour biology and has unmasked new molecular targets that may lead to the design of better anti-cancer therapies. Recently, using a high resolution loss of heterozygosity (LOH) analysis, we identified a number of potential tumour suppressor genes (TSGs) within common LOH regions across cases suffering from two of the most common forms of Non-Hodgkin's lymphoma (NHL), Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a common event in the lymphomagenesis of these B-cell lymphomas. The present study aimed to determine the cellular pathways affected by the inactivation of these TSGs including PTPRJ in FL and DLBCL tumourigenesis. Pathway analytical approaches identified that candidate TSGs located within common LOH regions participate within cellular pathways, which may play a crucial role in FL and DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated in NHL may play an important role in tumourigenesis. We also detected genes that are differentially expressed in cases with and without LOH of PTPRJ, such as NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events causing inactivation of PTPRJ, apart from possibly inducing a constitutive activation of these pathways by reduction or abrogation of its dephosphorylation activity, may also induce upregulation of these pathways when inactivated. This finding implicates these pathways in the lymphomagenesis and progression of FL and DLBCL. The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell tumours and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours.


Continuous thermal hydrolysis and energy integration in sludge anaerobic digestion plants.
A thermal hydrolysis pilot plant with direct steam injection heating was designed and constructed. In a first period the equipment was operated in batch to verify the effect of sludge type, pressure and temperature, residence time and solids concentration. Optimal operation conditions were reached for secondary sludge at 170 degrees C, 7 bar and 30 minutes residence time, obtaining a disintegration factor higher than 10, methane production increase by 50% and easy centrifugation In a second period the pilot plant was operated working with continuous feed, testing the efficiency by using two continuous anaerobic digester operating in the mesophilic and thermophilic range. Working at 12 days residence time, biogas production increases by 40-50%. Integrating the energy transfer it is possible to design a self-sufficient system that takes advantage of this methane increase to produce 40% more electric energy.


Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity.
Alcohol Use Disorder (AUD) contributes significantly to global mortality. GLP-1 (Glucagon-like peptide-1) and GLP-1/GIP (Glucose-dependent Insulinotropic Polypeptide) agonists, FDA-approved for managing type 2 diabetes and obesity, where the former has shown to effectively reduce the consumption of alcohol in animal models but no reports exist on the latter. In this report, we conducted two studies. In the first study, we conducted an analysis of abundant social media texts. Specifically, a machine-learning based attribution mapping of ~ 68,250 posts related to GLP-1 or GLP-1/GIP agonists on the Reddit platform. Secondly, we recruited participants (n = 153; current alcohol drinkers; BMI ≥ 30) who self-reported either taking Semaglutide (GLP-1 agonist), Tirzepatide (the GLP-1/GIP combination) for ≥ 30 days or, as a control group; no medication to manage diabetes or weight loss for a within and between subject remote study. In the social media study, we report 8 major themes including effects of medications (30%); diabetes (21%); and Weight loss and obesity (19%). Among the alcohol-related posts (n = 1580), 71% were identified as craving reduction, decreased desire to drink, and other negative effects. In the remote study, we observe a significantly lower self-reported intake of alcohol, drinks per drinking episode, binge drinking odds, Alcohol Use Disorders Identification Test (AUDIT) scores, and stimulating, and sedative effects in the Semaglutide or Tirzepatide group when compared to prior to starting medication timepoint (within-subjects) and the control group (between-subjects). In summary, we provide initial real-world evidence of reduced alcohol consumption in people with obesity taking Semaglutide or Tirzepatide medications, suggesting potential efficacy for treatment in AUD comorbid with obesity.


[Hearing defects after purulent meningitis (author's transl)].
80 children in the age of 4 to 20 years who got over a purulent meningitis in infancy or childhood were examined by means of several audiological methods. Two children (2,5 percent) were found to be deaf. In 4 cases (5 percent) deafness was detected only unilateral not preferring the right or left ear. Hearing impairment after the eights cranial nerve damage was found in four children. 4 children suffered from severe to profound hearing defects on one side or bilateral. No correlation could be found between incidence and severity of the hearing defects to the total dose of the antibiotics that were penicillin, ampicillin and gentamycin. Before the background of the literature reported on this subject and the presented results hearing impairment after purulent meningitis seems to be more likely a sequela of inflammation than a toxic side-effect of the antibiotics.


Balloon embolectomy catheters in small arteries. III. Surgical significance of eccentric balloons.
Some embolectomy balloons distend eccentrically. This study was undertaken to compare balloon eccentricity in air with that which occurs in arteries, to determine the influence of balloon eccentricity on shear force, and to estimate the injury potential of eccentric balloons. We studied 21 Edwards and 17 Shiley catheters in 24 dog carotid arteries in vitro. Each vessel was mounted horizontally in a Krebs-Ringer bath with one end of the vessel suspended from a force gauge. Catheters were inserted through an arteriotomy, and balloons were distended to lateral wall pressures of 25, 75, and 125 mm Hg. X-ray studies were used to measure balloon eccentricity--that is, the ratio of larger radius (R) to smaller radius (r). Comparison revealed a high correlation (r = 0.88, P less than 0.05) between R/r values in air and R/r values within arteries. Shear forces were produced when balloons were withdrawn through arteries. Regression equations revealed that the shear force increased about 10% for each unit increase in R/r. However, extremely eccentric balloons (R/r 8:1) pushed the catheter shaft deep into the vessel wall, gouging a linear tear in the media. This was seen in vitro and in two dogs studied 2 and 14 days after embolectomy. We conclude that balloon eccentricity in air is an accurate indicator of balloon eccentricity within arteries, that moderately eccentric balloons (R/r 3:1) are acceptable for clinical use, but that extremely eccentric balloons (R/r greater than 3:1) may cause severe injury and should not be used in the operating room.


[Exudative enteropathy and interstitial cystitis due to systemic lupus erythematosus].
A 33-year-old woman presented with chronic diarrhea, vomiting and anasarca due to systemic lupus erythematosus with protein-losing enteropathy, interstitial cystitis and glomerulonephritis. Methylprednisolone could not prevent aggravation of diarrhea, obstructive uropathy, and nephrotic syndrome, and prolonged intestinal ileus developed. Because of this steroid-resistance, bolus injections of cyclophosphamide (1 g i.v. monthly) were decided. Protein-losing enteropathy and ileus both disappeared rapidly following the first injection. Protein-losing enteropathy, intestinal ileus and interstitial cystitis are exceptional manifestations of systemic lupus erythematosus; steroid-resistance of the digestive manifestations has only been reported in one case and our observation is the first reporting the efficacy of cyclophosphamide.


Fast field cycling NMR relaxometry as a tool to monitor Parmigiano Reggiano cheese ripening.
It is widely recognized that the longer the ageing, the more valuable Parmigiano Reggiano (PR) cheese becomes, due to the improvement of its sensorial and nutritional properties. Up to now, the evaluation of PR properties has been performed on samples mainly aged up to 40 months. For this reason, this study was aimed at collecting information about the chemical-physical characteristics of PR cheeses after ageing at 24, 48 and 84 months. The basic analyses on water amount, protein content and volatile organic compounds (VOC) revealed that PR ageing is associated to the decomposition of the organic components into smaller units. This drives water molecules closer to the aforementioned units, thereby leading to a reduction of water activity. Moreover, it appears, from VOC investigation, that either the total amount of long chain fatty acids (LCFA) or the sole 9Z-octadecenoic acid considerably increased with PR aging, thereby making these molecular systems good fingerprint to monitor PR ripening. Fast field cycling (FFC) NMR relaxometry revealed different components of the molecular dynamics in the complex PR cheese samples, which were attributed to water trapped in casein micelles, water bound to polar groups in organic components, proteins, and fats. In particular, the reduction of the correlation times associated to the organic components was explained by the molecular size decrement following degradation processes. The ageing-independent component of the motion was assigned to water molecules bound to polar groups in organic moieties. Finally, the ageing-independent contribution to the overall relaxation rate was assigned to water molecules in casein micelles. This study revealed that FFC NMR relaxometry can be a promising technique to monitor the chemical physical changes during Parmigiano Reggiano cheese ripening.


Conserved Residues at the Mtr4 C-Terminus Coordinate Helicase Activity and Exosome Interactions.
Mtr4 is an essential RNA helicase involved in nuclear RNA processing and degradation and is a member of the Ski2-like helicase family. Ski2-like helicases share a common core architecture that includes two RecA-like domains, a winged helix, and a helical bundle (HB) domain. In Mtr4, a short C-terminal tail immediately follows the HB domain and is positioned at the interface of the RecA-like domains. The tail ends with a SLYΦ sequence motif that is highly conserved in a subset of Ski2-like helicases. Here, we show that this sequence is critical for Mtr4 function. Mutations in the C-terminus result in decreased RNA unwinding activity. Mtr4 is a key activator of the RNA exosome complex, and mutations in the SLYΦ motif produce a slow growth phenotype when combined with a partial exosome defect in S. cerevisiae, suggesting an important role of the C-terminus of Mtr4 and the RNA exosome. We further demonstrate that C-terminal mutations impair RNA degradation activity by the major RNA exosome nuclease Rrp44 in vitro. These data demonstrate a role for the Mtr4 C-terminus in regulating helicase activity and coordinating Mtr4-exosome interactions.