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Societal impact statement: This investigation addresses the diversity of microbial endosymbionts in cranberry, which are among the least understood and ill‐defined ericoid symbionts. There is excellent potential for Ericaceous plants, such as cranberry and blueberry, to be farmed more sustainably once the properties and functioning of their associated microbiomes are known in more detail. Here, we demonstrate that some bacterial and fungal endosymbionts of cranberry stimulate plant growth and suppress fungal pathogens. They have the potential for field applications as a first step toward sustainable cranberry farming. Summary: Virtually, all vascular plants harbor bacterial and fungal endosymbionts, which colonize predominantly but not exclusively, roots. Most common among fungal partners are arbuscular mycorrhizal fungi (AMF; Glomeromycotina) that live within plant roots and provide soil nutrients to the plant while receiving from the plant organic carbon sources. Ericaceae are an exception as they do not host AMF but rather the taxonomically ill‐defined "ericoid mycorrhizal fungi," including select ascomycete and basidiomycete species. Because the diversity of endosymbionts in Ericaceae is poorly investigated, we set out to explore the microbiome of Vaccinium macrocarpon Aiton (cranberry).Here, we report the isolation and ribotyping of ~180 distinct bacterial and fungal endophytes collected from roots, stems, and leaves of cranberry plants cultivated in Quebec, Canada. Plant growth promotion was assessed after inoculating plant cuttings with these microbes, whereas pathogen suppression was tested on agar plates by growth confrontation.We show that the cranberry microbiome varies substantially between tissues, cultivars, and across fields of the same farm. Among the isolates, 16 bacterial and 8 fungal strains exhibit biofertilization or biocontrol properties with potential application in sustainable cranberry farming.We propose to move towards a more rigorous, molecular‐based definition of ericoid mycorrhiza, accounting for their broad evolutionary and morphological diversity. [ABSTRACT FROM AUTHOR]

Aims: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a life‐threatening condition often associated with highly raised serum antibodies to glycine receptors (GlyRs); these bind to the surface of large neurons and interneurons in rodent brain and spinal cord sections and, in vitro, inhibit function and reduce surface expression of the GlyRs. The effects in vivo have not been reported. Methods: Purified plasma IgG from a GlyR antibody‐positive patient with PERM, and a healthy control (HC), was injected daily into the peritoneal cavity of mice for 12 days; lipopolysaccharide (LPS) to open the blood–brain barrier, was injected on days 3 and 8. Based on preliminary data, behavioural tests were only performed 48 h post‐LPS on days 5–7 and 10–12. Results: The GlyR IgG injected mice showed impaired ability on the rotarod from days 5 to 10 but this normalized by day 12. There were no other behavioural differences but, at termination (d13), the GlyR IgG‐injected mice had IgG deposits on the neurons that express GlyRs in the brainstem and spinal cord. The IgG was not only on the surface but also inside these large GlyR expressing neurons, which continued to express surface GlyR. Conclusions: Despite the partial clinical phenotype, not uncommon in passive transfer studies, the results suggest that the antibodies had accessed the GlyRs in relevant brain regions, led to antibody‐mediated internalization and increased GlyR synthesis, compatible with the temporary loss of function. [ABSTRACT FROM AUTHOR]

Aims: Bioequivalence (BE) trials aim to demonstrate that the 90% confidence interval of the T/R‐ratio of the pharmacokinetic metrics between two formulations (test [T] and reference [R]) of a drug is fully included in the acceptance interval [0.80, 1.25]. Traditionally, the sample size of BE trials is based on a power calculation based on the intrasubject variability coefficient of variation (CV) and the T/R‐ratio of the metrics. Since the exact value of the T/R‐ratio is not known prior to the trial, it is often assumed that the difference between the treatments does not exceed 5%. Hence, uncertainty about the T/R‐ratio is expressed by using a fixed value for the sample size calculation. We propose to characterise the uncertainty about the T/R‐ratio by a (normal) distribution for the log(T/R‐ratio), with an assumed mean of  log θ = 0.00 (i.e. θ = 1.00) and a standard deviation σu, which quantifies the uncertainty. Evaluating this distribution leads to the statistical assurance of the BE trial. Methods: The assurance of a clinical trial can be derived by integrating the power over the distribution of the input parameters, in this case, the assumed distribution of the log(T/R)‐ratio. Because it is an average power, the assurance can be interpreted as a measure of the probability of success that does not depend on a specific assumed value for the log(T/R)‐ratio. The relationship between power and assurance will be analysed by comparing the numerical outcomes. Results: Using the assurance concept, values of the standard deviation for the distribution of potential log(T/R)‐ratios can be chosen to reflect the magnitude of uncertainty. For most practical cases (i.e. when 0.95 ≤ θ ≤ 1.05), the sample size is not, or only slightly, changed when σ = |log(θ)|. Conclusion: The advantage of deriving the assurance for BE trials is that uncertainty is directly expressed as a parameter of variability. [ABSTRACT FROM AUTHOR]

Background and purpose: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico‐pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma‐associated myasthenia. Methods: A total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell‐surface proteins and cell‐based assays for contactin‐associated protein 2 (CASPR2), leucine‐rich glioma inactivated 1 (LGI1), glycine receptor and Netrin‐1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2. Results: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin‐1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93–0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38–48.36) and neuromyotonia (OR 41.78, 95% CI 4.71–370.58). Conclusions: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG. [ABSTRACT FROM AUTHOR]

Background Smoking is a strong environmental factor leading to adverse outcomes in Crohn's disease, but a more benign course in ulcerative colitis. Several single nucleotide polymorphisms ( SNPs) are associated with smoking quantity and behaviour. Aim To assess whether smoking-associated SNPs interact with smoking to influence the clinical course of inflammatory bowel diseases. Methods Genetic and prospectively obtained clinical data from 1434 Swiss inflammatory bowel disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were analysed. Six SNPs associated with smoking quantity and behaviour (rs588765, rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a risk score (range: 0-12) by adding the number of risk alleles. We calculated multivariate models for smoking, risk of surgery, fistula, Crohn's disease location and ulcerative colitis disease extent. Results In Crohn's disease patients who smoke, the number of surgeries was associated with the genetic risk score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to 5.7-fold, P<.0001) higher number of surgical procedures in smokers with 12 risk alleles than individuals with the lowest risk. Patients with a risk score >7 had a significantly shorter time to first intestinal surgery. The genetic risk score did not predict surgery in ulcerative colitis or occurrence of fistulae in Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease ( P<.05) and proctitis in ulcerative colitis ( P<.05). Conclusions SNPs associated with smoking quantity is associated with an increased risk for surgery in Crohn's disease patients who smoke. Our data provide an example of genetics interacting with the environment to influence the disease course of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background Autoantibodies directed against specific neuronal antigens are found in a significant number of patients with gastrointestinal neuromuscular diseases (GINMDs) secondary to neoplasia. This study examined the presence of antineuronal antibodies in idiopathic GINMD and GINMD secondary to South American Trypanosomiasis. The GI distribution of voltage-gated potassium channels (VGKCs) was also investigated. Methods Seventy-three patients were included in the study with diagnoses of primary achalasia, enteric dysmotility, chronic intestinal pseudo-obstruction, esophageal or colonic dysmotility secondary to Chagas' disease. Sera were screened for specific antibodies to glutamic acid decarboxylase, voltage-gated calcium channels (VGCCs; P/Q subtype), nicotinic acetylcholine receptors (nAChRs; α3 subtype), and voltage-gated potassium channels (VGKCs, KV1 subtype) using validated immunoprecipitation assays. The distribution of six VGKC subunits (KV1.1-1.6), including those known to be antigenic targets of anti-VGKC antibodies was immunohistochemically investigated in all main human GI tract regions. Key Results Three patients (14%) with chagasic GI dysmotility were found to have positive anti-VGKC antibody titers. No antibodies were detected in patients with idiopathic GINMD. The VGKCs were found in enteric neurons at every level of the gut in unique yet overlapping distributions. The VGKC expression in GI smooth muscle was found to be limited to the esophagus. Conclusions & Inferences A small proportion of patients with GI dysfunction secondary to Chagas' disease have antibodies against VGKCs. The presence of these channels in the human enteric nervous system may have pathological relevance to the growing number of GINMDs with which anti-VGKC antibodies have been associated. [ABSTRACT FROM AUTHOR]

Background: GQ1b antibody (GQ1b-Ab) is detected in approximately two-thirds of sera of patients with Bickerstaff’s encephalitis (BE). Whilst some of the remaining patients have antibodies to other gangliosides, many patients with BE are reported to be seronegative. Methods and Results: Voltage-gated potassium channel antibody (VGKC-Ab) at high titer was detected during the diagnostic work-up of one patient with BE. Sera of an additional patient with BE and nine patients with Miller Fisher syndrome (MF) (all GQ1b-Ab positive) were investigated for VGKC-Ab and other anti-neuronal antibodies by radioimmunoprecipitation using 125I-dendrotoxin-VGKC and immunohistochemistry, respectively. Two patients with MF exhibited moderate titer VGKC-Abs. Regardless of positivity for VGKC or GQ1b antibodies, serum IgG of all patients with BE and MF reacted with the molecular layer and Purkinje cells of the cerebellum in a distinctive pattern. Conclusion: Voltage-gated potassium channel antibodies might be involved in some cases of BE or MF. The common staining pattern despite different antibody results suggests that there might be other, as yet unidentified, antibodies associated with BE and MF. [ABSTRACT FROM AUTHOR]

Encephalitis lethargica (EL) describes an encephalitis with psychiatric, sleep, and extrapyramidal movement disorders. Dyskinetic and parkinsonian forms have been described. EL shares clinical features with the anti-N-methyl-D-aspartate receptor (NMDAR-Ab) encephalitis. We studied 20 sera from pediatric patients with contemporary EL. Ten sera (from 2 males and 8 females, aged 1.3-13 years) and 6/6 cerebrospinal fluid samples were positive for NMDAR-Ab. NMDAR-Ab-positive patients had dyskinesias, agitation, seizures, and insomnia, whereas parkinsonism and somnolence dominated in the NMDAR-Ab-negative children. We were unable to identify any tumors. The dyskinetic form of EL is an NMDAR-Ab encephalitis and can affect very young children. [ABSTRACT FROM AUTHOR]

In this article the author discusses the study on arbuscular mycorrhizal fungi (AMF) in various taxon. They state that nuclear genome sequencing of AMF entails not just simple deciphering of Mbp, average genome size within Glomus intraradices. Also examined is the first complete mitochondrial DNA (mtDNA) sequence of glomeromycete or G. intraradices .

Summary The induction of luminescence in Vibrio harveyi at the later stages of growth is controlled by a quorum-sensing mechanism in addition to nutritional signals. However, the mechanism of transmission of these signals directly to the lux promoters is unknown and only one regulatory protein, LuxR, has been shown to bind directly to lux promoter DNA. In this report, we have cloned and sequenced two genes, crp and metR , coding for the nutritional regulators, CRP (cAMP receptor protein) and MetR (a LysR homologue), involved in catabolite repression and methionine biosynthesis respectively. The metR gene was cloned based on a general strategy to detect lux DNA-binding proteins expressed from a genomic library, whereas the crp gene was cloned based on its complementation of an Escherichia coli crp mutant. Both CRP and MetR were shown to bind to lux promoter DNA, with CRP being dependent on the presence of cAMP. Expression studies indicated that the two regulators had opposite effects on luminescence: CRP was an activator and MetR a repressor . Disruption of crp decreased luminescence by about 1000-fold showing that CRP is a major activator of luminescence the same as LuxR, whereas disruption of MetR resulted in activation of luminescence over 10-fold, confirming its function as a repressor. Comparison of the levels of the autoinducers involved in quorum sensing excreted by V. harveyi, and the crp and metR mutants, showed that autoinducer production was not significantly different, thus indicating that the nutritional signals do not affect luminescence by changing the levels of the signals required for quorum sensing. Indeed, the large effects of these nutritional sensors show that luminescence is controlled by multiple signals related to the environment and the cell density which must be integrated at the molecular level to control expression at the lux promoters. [ABSTRACT FROM AUTHOR]

Studies calcium channel subtypes that contribute to acetylcholine release from normal, 4-amino-pyridine-treated and myasthenic syndrome auto-antibodies-affected neuromuscular junctions. Key issues of interest; Analysis of pertinent topics and relevant issues; Implications on pharmacology.

Although field biologists commonly employ methodologies that either are time-tested or are believed (usually for very good reason) to be suitable to the conditions that are encountered, it is rare that results generated using differing methods can be compared on a single fauna. We reanalyze data from three studies conducted on the small mammal fauna of Valdivian temperate rainforests in southern Chile. By restricting our analyses to a relatively homogeneous habitat type we avoid many problems associated with studies over large spatial scales, such as increased species richness via beta diversity. The studies involve a temporal transect, an elevational transect, and a latitudinal transect, and comprise a spatially nested series. Because these studies differed in their initial objectives, they employed different methodologies, both in the field and during subsequent data analysis. At all scales of analysis there is notable overlap in habitat use by all species. Although we observed some seasonal differences in habitat use by species, these were not substantial and involved a small subset of the species. At a local scale, numerically dominant species selected non-random microhabitats but co-occurred with other species more frequently than expected by chance. At a larger spatial scale species appeared to select large subsets of the macrohabitat (i.e, 'mesohabitat'), providing patterns suggestive of apparent competition among species. At an even larger spatial scale, that of temperate southern South America, we predict that species assemblages will again exhibit positive associations. Thus, views on the importance of competition andother biological processes depend critically on the spatial and temporal scales over which observations are made. [ABSTRACT FROM AUTHOR]

The currently used composite resin classification systems need review if they are to continue to serve as descriptives and quantitative parameters denoting the filler particle content of these materials. Examination of the particles in 12 composite resins using a technique of washing the filler particles from the matrix of the composite resin was presented as yet another method of grouping composites according to filler particle content. Light microscopic examination of the filler particles that remained provided a separation of the 12 materials into four easily distinguished groups based on filler particle sizes. The wear of the 12 composite resins determined in a previous study was examined in relation to the classification of the materials by the currently available systems. The wear values were also examined using the groupings of the materials according to their filler particle sizes as determined by separating the particles from the matrix by the washing technique. Grouping composites on the basis of the filler particle sizes found after washing was easily correlated with wear and supported the suggestion that composites with smaller filler particles wear less. [ABSTRACT FROM AUTHOR]

In eighteen subjects assigned for immediate complete upper and lower dentures, roentgen cephalometric recordings were made before extraction of the residual anterior dentition and 3 weeks, 3 months, 6 months and 1 year after denture insertion. The cephalometric analysis was based on electronic measurements of linear and angular morphological variables and computer head plots generated from 177 reference points (Walker, 1967), derived for each subject for each of the five observation stages. The reduction of the alveolar ridges was most rapid during the first 3 months of denture wear and particularly during the post-extraction period of 3 weeks. The reduction in anterior height of the lower ridge was on average twice as great as that of the upper ridge. The ridge resorption and the accompanying settling of the dentures on the basal seats, measured from lead shots inserted in the dentures, brought about an upward rotation of the mandible with a resulting decrease in occlusal vertical dimension and reduction in overjet of the dentures. In accordance with the amount of ridge reduction, these changes showed great individual variation.

To isolate a gene that can be used as internal control in studies on gene expression in Aplysia californica neurons, we have characterized a cDNA clone (pKRP-A) isolated on the basis of its high expression in A. californica neurons. This cDNA is of 850 nucleotides and codes for a putative 29-kDa lysine-rich protein. Blotting experiments revealed that the gene is expressed in all tested A. californica tissues, and in individually identified neurons of the abdominal ganglion, suggesting that this gene can be efficiently used as internal control in studies of gene expression. We have also isolated one cDNA and two different genomic clones from yeast libraries that show 59% identity with pKRP-A. Sequence comparison of genomic clones, as well as PCR and Southern blotting experiments, revealed that at least two homologous gene are present in yeast. Northern blotting experiments revealed that the expression of the gene is strongly repressed at 39°C. [ABSTRACT FROM AUTHOR]

The DNA sequence of the mitochondrial large subunit (LSU) rRNA gene of Schizosaccharomyces pombe has been determined. In the direction of transcription, this gene is located between the gene coding for subunit II of cytochrome oxidase and a cluster of three tRNA genes. Both the 5' and 3' ends of the LSU rRNA have been mapped precisely: whereas the 5' end can be assigned unambiguously to a single nucleotide position, multiple 3' ends occur within a run of eight U residues. Based on these results, the S. pombe LSU rRNA is between 2818 and 2826 nucleotides long. A sequence motif immediately upstream of the 5' end of the gene resembles that of the mitochondrial promoter motif of Saccharomyces cerevisiae; however, the sequence at the 3' end of the gene is not similar to any of the motifs implicated as processing signals in other mitochondrial systems. Unlike its counterparts in S. cerevisiae and Aspergillus nidulans, the mitochondrial LSU rRNA gene of S. pombe does not contain an intron. Comparison of potential secondary structure among the three fungal mitochondrial and Escherichia coli LSU rRNAs has defined a common secondary structure core, held together by long-range hydrogen-bonding interactions. A 5.8S-like structure is present within the 5'-terminal region of all three fungal mitochondrial LSU rRNAs; in contrast, no 4.5S-like structure is evident at the 3' end of these molecules. An evolutionary evaluation of highly conserved regions of a small set of LSU rRNA sequences suggests that S. pombe mitochondria diverged from a mitochondrial proto-fungal branch earlier than either A. nidulans or S. cerevisae mitochondria. This result, considered in conjunction with the patterns of genome organization and codon usage in fungal mitochondria, points to a slower evolutionary clock speed in the mitochondrial genome of S. pombe. [ABSTRACT FROM AUTHOR]

In a sample of fifteen partially edentulous subjects assigned for immediate complete denture treatment, a correlation analysis was performed between pre-extraction facial morphology determined from lateral cephalograms, and EMG activity of the anterior temporal and masseter muscles in maximal clench and tapping of teeth. Marked correlations observed between vertical and sagittal jaw relations and mean voltages of the jaw-closing muscles indicated strong biting activity in subjects with a square facial type. No significant associations were observed between biting strength and the age of the subjects. Correlations between facial morphological changes and changes in EMG biting activity after denture insertion and during 1 year of denture wear indicated that the anterior temporal muscles were extremely sensitive to sagittal changes in anterior occlusion. The masseter muscles were less sensitive, but responded in some instances to changes in vertical jaw relationship. [ABSTRACT FROM AUTHOR]

Mitachondrial gene sequences, in contrast to their plastid counterparts, have been rarely exploited for use in determining algal phylogenetic relationships. Their utilization would prove advantageous particularly for the assessment of evolutionary relationships among protistan lineages that include photosynthetic species and their colorless heterotrophic decendents that contain only a reduced plastid genome as well as ancestral nonphotosynthetic relatives. Recent studies that have examined mitochondrial protein (cox1, cox2, cob, and nad5) rather than ribosomal RNA genes confirm that these algal sequences are sufficiently conserved to be used routinely in algal systematics. In this investigatin, we sequenced the mitochondrial nad4L gene, encoding a small (ca.99-amino acid) polypeptide subunit of the NADH dehydrogenase complex, from two chromophytic algae and an comycete to determine its suitability for use in determining algal and protistau evolutionary relationships. Our analysis demonstrated that nad4L could clearly resolve these three organisms as a distinct clade, the stramenopiles, to the exclusin of terrestrial plants/chlorophytes and eufungi. However the position of deeply rooted species within the stramenopiles proved tenuous and would best be examined in conjuction with the analysis of longer mitochondrial protein gene sequence. [ABSTRACT FROM AUTHOR]

Background Treatment-resistant complex partial seizures ( CPS) with orofacial involvement recently were reported in cats in association with hippocampal pathology. The features had some similarity to those described in humans with limbic encephalitis and voltage-gated potassium channel ( VGKC) complex antibody. Hypothesis/Objectives The purpose of this pilot study was to evaluate cats with CPS and orofacial involvement for the presence of VGKC-complex antibody. Animals Client-owned cats with acute orofacial CPS and control cats were investigated. Methods Prospective study. Serum was collected from 14 cats in the acute stage of the disease and compared with 19 controls. VGKC-complex antibodies were determined by routine immunoprecipitation and by binding to leucine-rich glioma inactivated 1 ( LGI1) and contactin-associated protein-like 2 ( CASPR2), the 2 main targets of VGKC-complex antibodies in humans. Results Five of the 14 affected cats, but none of the 19 controls, had VGKC-complex antibody concentrations above the cut-off concentration (>100 pmol/L) based on control samples and similar to those found in humans. Antibodies in 4 cats were directed against LGI1, and none were directed against CASPR2. Follow-up sera were available for 5 cats in remission and all antibody concentrations were within the reference range. Conclusion and Clinical Importance Our study suggests that an autoimmune limbic encephalitis exists in cats and that VGKC-complex/ LGI1 antibodies may play a role in this disorder, as they are thought to in humans. [ABSTRACT FROM AUTHOR]

Presents an abstract of the study 'A Comparative Study of Unilateral and Bilateral Endoscopic Extraperitoneal (EEP) Inguinal Hernioplasties.'

The article presents the authors' response to an insightful comments to their genome-wide research examining the relationship between genetic variants in tobacco smoke and disease status of patients with inflammatory bowel disease (IBD).

Presents a study on the association between voltage gated calcium channel (VGCC) antibodies and small cell lung cancer patients. Role of VGCC antibodies in the Lambert Eaton myasthenic syndrome; Detection of antibodies by radioimmunoassay.

Aim: The absence of consensus regarding the presence and interpretation of certain symptoms as indicative of either a psychosis spectrum disorder or an eating disorder (ED) can hinder cooperation amongst treatment programmes for the early detection of psychosis and an ED. This study trans-diagnostically assessed the prevalence and co-occurrence of at-risk mental states for a psychosis (ARMS) or the risk of having an ED (EDr), and it explored the characteristics of ARMS profiles of individuals with an EDr., Method: This cross-sectional and observational-prevalence study used assessment outcomes from an ED screening instrument (SCOFF), a psychosis prodromal screening questionnaire (PQ16) and a CAARMS interview (to evaluate the possibility of ARMS) with newly admitted outpatients aged 16-35 who were referred for various kinds of non-psychotic disorders from a secondary Mental Health Care Centre in the Netherlands. Data analysis consisted of calculating prevalences, associations amongst variables and conditional probabilities., Results: Of the 736 individuals who were screened, an EDr was identified in 51.2% and 49.0% of the participants who scored high on the PQ16, half of whom also completed the CAARMS interview. The results indicated that 53.0% of the participants were classified as not having ARMS, 28.3% as having ARMS and 18.7% as having a psychosis. EDr patients presented with symptoms of a psychotic spectrum disorder, which included both ED-consistent and ED-inconsistent symptoms. There were relatively frequent endorsements of the two subscale items guilt/punishment and ideas of reference., Conclusions: From a trans-diagnostical perspective, the results indicate that collaboration amongst ED programmes and psychosis prevention interventions should be strongly encouraged. Future researchers are encouraged to conduct studies that assess associations amongst and features of psychotic spectrum symptoms in EDs. The unexpectedly high proportion of EDr suggests that a co-morbid ED in other kinds of psychopathology is being overlooked., (© 2024 John Wiley & Sons Australia, Ltd.)

Introduction: Alcohol beverages in many countries are required to display health information and warnings on all product packaging, given the individual and societal harm caused by alcohol. It is unclear whether consumers purchasing alcohol online are able to easily view such information. This study examines the presence, type and location of mandatory and voluntary health information and warnings consumers are exposed to when entering online alcohol retail shopping environments in the United Kingdom (UK) and New Zealand (NZ)., Methods: Using an observational study design, 1407 randomly sampled alcoholic beverages from 14 online alcohol retailers (7 per country) were reviewed to ascertain the visual presence or absence of mandatory and voluntary health information and warnings., Results: UK online alcohol retailers were more compliant than NZ retailers in showing mandatory health information (e.g., alcohol by volume percentage was visible on 92% of alcoholic beverages sold online in the UK, compared to 31% in NZ, p < 0.001). A similar pattern was noted for voluntary health warnings. Online retailers in both countries had a low proportion of alcohol products with the viewable mandatory information, and voluntary health warnings were rarely present and/or viewable., Discussion and Conclusions: Mandatory health information and warnings for alcoholic beverages are not fully adhered to within the UK and NZ online retail environments, impacting the ability of consumers to make informed purchase decisions. In both countries, alcohol policy needs to stipulate that mandatory health information and warnings should be clearly viewable on the product page and product imagery of online alcohol retailers., (© 2022 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Background: The present study with trial sequential analysis (TSA) was conducted to evaluate comprehensively the efficacy and safety of dexmedetomidine and midazolam in pediatric sedation, and to investigate whether the outcomes achieved the required information size to draw the conclusions., Methods: PubMed, Embase, and Cochrane Library were searched from inception to October 2019. All randomized controlled trials used dexmedetomidine and midazolam in pediatric sedation were enrolled. Sedative efficacy, postoperative analgesic effect, and incidence of emergence agitation were considered as the co-primary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to rate the quality of evidences., Results: We acquired data from 34 studies involving 2281 pediatric patients. The results indicated that administration of dexmedetomidine was associated with less incidence of emergence agitation (RR = 0.78, with 95% CI [0.65, 0.92]) and more satisfactory sedation at parental separation (RR = 0.31, with 95% CI [0.24, 0.41]) compared to midazolam, and the current sample sizes were sufficient with unnecessary further trials. Two groups did not differ significantly in sedation level at mask induction (RR = 0.86, with 95% CI [0.74, 1.00]). And using of dexmedetomidine was associated with less incidence of postoperative analgesic rescue (RR = 0.57, with 95% CI [0.35, 0.93]), but the number of patients was too few to achieve the required information size and to draw reliable conclusions. Premedication of dexmedetomidine was associated with significant less value of SBP, heart rate, increased incidence of bradycardia, and a lower rate of shivering. And there were no differences about onset of sedation and recovery time between two groups., Conclusions: Given that more satisfactory sedation at separation from parents and less incidence of emergence agitation, dexmedetomidine is preferred for pediatric sedation. However, compared with midazolam, the superiority of dexmedetomidine in providing adequate sedation at mask induction and postoperative analgesic effects has not yet been defined., (© 2020 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aims: Idarucizumab, a humanized monoclonal anti-dabigatran antibody fragment, is effective in emergency reversal of dabigatran anticoagulation. Pre-existing and treatment-emergent anti-idarucizumab antibodies (antidrug antibodies; ADA) may affect the safety and efficacy of idarucizumab. This analysis characterized the pre-existing and treatment-emergent ADA and assessed their impact on the pharmacokinetics and pharmacodynamics (PK/PD) of idarucizumab., Methods: Data were pooled from three Phase I, randomized, double-blind idarucizumab studies in healthy Caucasian subjects; elderly, renally impaired subjects; and healthy Japanese subjects. In plasma sampled before and after idarucizumab dosing, ADA were detected and titrated using a validated electrochemiluminescence method. ADA epitope specificities were examined using idarucizumab and two structurally related molecules. Idarucizumab PK/PD data were compared for subjects with and without pre-existing ADA., Results: Pre-existing ADA were found in 33 out of 283 individuals (11.7%), seven of whom had intermittent ADA. Titres of pre-existing and treatment-emergent ADA were low, estimated equivalent to <0.3% of circulating idarucizumab after a 5 g dose. Pre-existing ADA had no impact on dose-normalized idarucizumab maximum plasma levels and exposure and, although data were limited, no impact on the reversal of dabigatran-induced anticoagulation by idarucizumab. Treatment-emergent ADA were detected in 20 individuals (19 out of 224 treated [8.5%]; 1 out of 59 received placebo [1.7%]) and were transient in ten. The majority had specificity primarily toward the C-terminus of idarucizumab. There were no adverse events indicative of immunogenic reactions., Conclusion: Pre-existing and treatment-emergent ADA were present at extremely low levels relative to the idarucizumab dosage under evaluation. The PK/PD of idarucizumab appeared to be unaffected by the presence of pre-existing ADA., (© 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: To investigate P- and E-selectin ligand coexpression with chemokine receptors (CKRs) on T cells in the synovial fluid (SF) and blood of children with juvenile idiopathic arthritis (JIA)., Methods: Sixteen patients with polyarticular or persistent oligoarticular JIA (ages 5.3-15.1 years) were studied. SF and venous blood were collected, and immunostaining for the expression of CCR4, CCR5, CXCR3, and P- or E-selectin ligands was performed., Results: Compared to blood, SF was greatly enriched for CD4+ T cells bearing CCR5, CCR4, CXCR3, and both P- and E-selectin ligand. Twenty-five percent of the CD4+ T cells in SF expressed both CCR5 and CCR4, some also coexpressing CXCR3. Such cells were rare in blood. Half of the few CCR5+ T cells in blood coexpressed P- or E-selectin ligand, a phenotype that was enriched up to 50-fold in SF. A minority of CCR4+ and CXCR3+ cells in blood (∼25%) coexpressed selectin ligand; these were enriched 4-8-fold in SF. Most CCR4-expressing CD4+ T cells expressed both E-selectin ligand and cutaneous lymphocyte antigen., Conclusion: CCR4-, CCR5-, CXCR3-, and selectin ligand-expressing CD4+ T cells preferentially accumulate in the joints of children with JIA. The marked enrichment of CCR5+ T cells coexpressing P-selectin and/or E-selectin ligand in CD4+ SF T cells suggests that the few such cells in blood selectively migrate to inflamed joints via endothelial P- and E-selectin- and CCR5-activating chemokines. The predominance of CCR4-expressing CD4+ T cells coexpressing E-selectin ligand suggests that such cells migrate not only to areas of cutaneous inflammation, as previously reported, but also to the joints in JIA. Combined targeting of CCR5- and E-selectin-dependent mechanisms may be a relevant treatment strategy., (Copyright © 2011 by the American College of Rheumatology.)

Objective: To determine early predictors of 6-month outcomes in a prospective cohort of patients with juvenile idiopathic arthritis (JIA)., Methods: Patients selected were those enrolled in an inception cohort study of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study, within 6 months after diagnosis. The juvenile rheumatoid arthritis core criteria set and quality of life measures were collected at enrollment and 6 months later. Outcomes evaluated included inactive disease, Juvenile Arthritis Quality of Life Questionnaire (JAQQ) scores, and Childhood Health Assessment Questionnaire (C-HAQ) scores at 6 months., Results: Thirty-three percent of patients had inactive disease at 6 months. Onset subtype and most baseline core criteria set measures correlated with all 3 outcomes. Relative to oligoarticular JIA, the risks of inactive disease were lower for enthesitis-related arthritis, polyarthritis rheumatoid factor (RF)-negative JIA, and polyarthritis RF-positive JIA, and were similar for psoriatic arthritis. In multiple regression analyses, the baseline JAQQ score was an independent predictor of all 3 outcomes. Other independent baseline predictors included polyarthritis RF-negative and systemic JIA for inactive disease; C-HAQ score and polyarthritis RF-positive JIA for the 6-month C-HAQ score; and active joint count, pain, and time to diagnosis for the 6-month JAQQ score., Conclusion: Clinical measures soon after diagnosis predict short-term outcomes for patients with JIA. The JAQQ is a predictor of multiple outcomes. Time to diagnosis affects quality of life in the short term.

Objective: To determine the bone mineral density (BMD) status of our juvenile dermatomyositis (DM) population and to compare the frequency of osteopenia in patients with active disease requiring corticosteroids with that in patients with inactive disease who are not receiving corticosteroids., Methods: Medical charts of all children diagnosed as having juvenile DM at our institution between 1989 and 1999 were reviewed for demographic and clinical data, including disease activity and duration of corticosteroid therapy. BMD measurements of the lumbar spine (L1-L4) were performed using dual x-ray absorptiometry (DXA). Z scores were calculated from the BMD data for comparison with published normative data., Results: A total of 15 patients were assessed: 10 with active disease, and 5 with inactive disease who had not taken corticosteroids for an average of 6.0 years (range 3.4-8.1 years). Baseline BMD measurements demonstrated osteopenia or frank osteoporosis in the majority of patients, including 6 of the 10 patients with active disease and 4 of the 5 patients whose disease was in remission. Fourteen patients had serial BMD measurements. Persistent or worsening osteopenia was documented in all patients who had ongoing active disease, except for 3 patients who had been treated with bisphosphonates because of vertebral compression fractures., Conclusion: Osteopenia is common in patients with juvenile DM, and it usually worsens with ongoing disease. It can persist for many years after the disease enters remission. Bisphosphonates appeared to beneficially affect bone mineralization in our patients. Treatment to prevent the long-term complications of osteoporosis in patients with juvenile DM should be considered and requires further study.