Infancy and pediatric cancer: an exploratory study of parent psychological distress.

BACKGROUND: Research on the psychological experiences of parents of infants within pediatric oncology is sparse. This study examined rates and indicative risk factors for psychological distress in parents where there is either an infant patient or infant sibling of a patient. METHODS: Participants were mothers (n = 41) and fathers (n = 25) of infants under 2 years who either had a cancer diagnosis (n = 37; infant patients) or was an infant sibling of an older child with cancer (n = 29; infant siblings) recruited from a single oncology center. There were 21 couple dyads. Parents completed the Depression Anxiety Stress Scales short form and the Posttraumatic Stress Disorder Checklist. RESULTS: Mothers (47.5%) and fathers (37.5%) reported elevated, cancer-related posttraumatic stress symptoms. Rates of depression (12.2% of mothers and 12.0% of fathers) and anxiety symptoms (17.1% of mothers and 8.0% of fathers) were lower. Compared with parents of infant patients, parents of infant siblings reported significantly higher rates of depressive symptoms and trends toward higher rates of posttraumatic stress symptoms and anxiety symptoms. Parent anxiety was higher with increased time post diagnosis. No demographic or illness-related variables were associated with psychological distress, with the exception of the number of children in the family. CONCLUSIONS: Parent-child relationships are of fundamental importance during infancy. This study provides novel data highlighting the psychological impact for parents when a cancer diagnosis is made during this critical developmental period, including the contribution of family structure to parental distress. Results provide further support for applying a traumatic stress framework when exploring parent experiences of pediatric cancer. Copyright © 2016 John Wiley & Sons, Ltd.

Survey of captive parrot populations around Port Phillip Bay, Victoria, Australia, for psittacine beak and feather disease virus, avian polyomavirus and psittacine adenovirus.

OBJECTIVE: This study investigated the prevalence of psittacine beak and feather disease virus (BFDV), avian polyomavirus (APV) and psittacine adenovirus (PsAdV) in captive psittacine birds around Port Phillip Bay, Victoria, Australia. METHODS: Samples of fresh droppings were collected from 118 psittacine birds (109 clinically normal and 9 with feather abnormalities) from 11 avaries in different locations and were used for detection of BFDV, APV and PsAdV using PCR. RESULTS: BFDV, APV and PsAdV were detected in 31%, 13% and 4%, respectively, of the specimens tested. One budgerigar was found to be co-infected with BFDV and PsAdV. At least one sample tested positive for BFDV at each location. CONCLUSION: This is the first report of the prevalence of BFDV, APV and PsAdV in Victoria and provides a foundation for future studies examining the influence of these viruses on the health of aviary birds in Victoria.

B cell specificity contributes to the outcome of diabetes in nonobese diabetic mice.

Type I diabetes mellitus (TIDM) is an autoimmune disorder characterized by T cell-mediated destruction of insulin-producing beta cells in the pancreas. In the nonobese diabetic (NOD) model of TIDM, insulitis and diabetes are dependent on the presence of B lymphocytes; however, the requirement for specificity within the B cell repertoire is not known. To determine the role of Ag-specific B cells in TIDM, V(H) genes with different potential for insulin binding were introduced into NOD as H chain transgenes. VH125 H chain combines with endogenous L chains to produce a repertoire in which 1-3% of mature B cells are insulin specific, and these mice develop accelerated diabetes. In contrast, NOD mice harboring a similar transgene, VH281, with limited insulin binding develop insulitis but are protected from TIDM. The data indicate that Ag-specific components in the B cell repertoire may alter the course of TIDM.

Cognitively oriented psychotherapy for early psychosis (COPE): a 1-year follow-up.

OBJECTIVES: Cognitively oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the adjustment of the person, and at preventing or alleviating secondary morbidity in the wake of the first psychotic episode. DESIGN: A total of 80 people participated in the initial trial and completed assessments on a range of outcome measures. Post-treatment assessment results from a non-randomized controlled trial of COPE have been previously reported. The present paper describes the results obtained from 51 patients who attended a follow-up assessment 1 year subsequent to the end-of-treatment assessment. METHOD: The 51 patients formed three groups: (1) those who were offered and accepted COPE; (2) those who were offered COPE but refused it, and continued to receive other services from the Early Psychosis Prevention and Intervention Centre (EPPIC) (refusal subjects); and (3) those who were offered neither COPE nor any other continuing treatment from EPPIC (control subjects). RESULTS: At 1-year follow-up, there was only one significant difference and this was between the COPE and refusal groups on the Integration/Sealing Over (I/SO) measure (p = .008). End-of-treatment differences were mostly sustained over the 1-year follow-up period. When the complete sample of 80 was considered, there were no differences between the three groups in terms of hospital admissions, community episodes, or time taken to first in-patient re-admission. CONCLUSIONS: The study was weakened by the poor follow-up rates in the two control groups. This reduced power to detect differences between groups on the seven major measures. However, the relapse data gathered on the complete set of 80 patients were discouraging and suggest that the present formulation of COPE does not confer any advantage to those patients receiving the therapy over those not receiving the therapy.

Anergy and not clonal ignorance determines the fate of B cells that recognize a physiological autoantigen.

Autoantibodies to insulin arise spontaneously in the insulin autoimmune syndrome and in type I diabetes. In addition, administration of insulin to individuals without autoimmune disease routinely results in Abs that bind autologous hormone. These observations and findings in transgenic models of tolerance led to an inference that physiological levels of hormones and growth factors, such as insulin, are not sufficient to induce tolerance in B cells, a state termed clonal ignorance. In contrast, we have discovered that virtually all conventional B cells expressing a low affinity anti-insulin transgene interact with endogenous insulin and are effectively silenced for Ig production and for T cell-dependent immune responses. A fraction of transgenic B cells escapes silencing and functions autonomously to produce insulin Abs that may lower fasting blood sugars similar to an insulin autoimmune syndrome. These B cells have characteristics of a B1-like subset and are depleted by hypotonic peritoneal lysis. These findings question the concept of clonal ignorance and show that physiological concentrations of Ag may effectively silence conventional B cells even when the affinity for autoantigen is low. Self-reactivity may arise in the repertoire because of compartmental differences that govern the fate of B cells and not as a result of true clonal ignorance.

Cognitively-oriented psychotherapy for early psychosis (COPE). Preliminary results.

BACKGROUND: The present study describes the results of the pilot testing of a therapy we have developed for people with first-episode psychosis. Cognitively-oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the adjustment of the person, and at preventing or alleviating secondary morbidity in the wake of the first psychotic episode. METHOD: Eighty people formed three groups: those who were offered and accepted COPE (COPE subjects); those who refused COPE (refusal subjects); and those who were offered neither COPE nor any other continuing treatment from our service (control subjects). The individuals were assessed prior to, and at the end of, COPE treatment (a 12-month period) on the Integration/Sealing Over, Explanatory Model, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, Quality of Life, SCL-90-R, and Beck Depression Inventory measures. RESULTS: People who received COPE obtained significantly superior scores (P < 0.05) to the control group on four of the seven measures but only significantly out-performed the refusal group on one of the seven measures (P < 0.05). The COPE group performed significantly worse on the BDI than the refusal group (P < 0.05). Effect sizes are also provided for each measure. CONCLUSIONS: There seems to be a place for psychological therapy in this group of people but our results need to be replicated in a more definitive randomised controlled trial and such a study is now in progress.

Somatically mutated B cell pool provides precursors for insulin antibodies.

Antibodies to insulin are products of autoreactive B lymphocytes that escape inactivation or clonal deletion and are examples of "clonal ignorance." To understand the genetic origin of Abs from clonally ignorant B cells, the roles of somatic mutation and germ-line V(H) structures were examined for two murine IgG1 mAb that bind human and rodent insulin. Engineered mAb constructs that express germ-line or mutated V(H) genes show that somatic mutations introducing aspartic acid in or adjacent to CDRH2 play a key role in insulin binding. When either of the two anti-insulin V(H) regions is returned to its germ-line (unmutated) sequence, neither mAb binds insulin and the germ-line-encoded mAb are not polyreactive. Reconstruction of the somatic evolution of insulin binding in both mAbs shows that a single mutation in CDRH2 is sufficient to generate anti-insulin activity from a nonbinding precursor. When the role of somatic mutation in the binding of rodent insulin is examined, autoreactivity is associated with single mutations in both Abs. Together these findings indicate that, despite a low mutation frequency, IgG insulin Abs may not be derived directly from germ-line (unmutated) precursors. The requirement for somatic mutation as a prerequisite for measurable insulin binding suggests these Abs have their origin in a previously mutated B cell pool as a consequence of the individual's immune history. Low avidity interaction with endogenous insulin may play a role in selection of these B cells and contribute to the origin of clonal ignorance.

Dynamic changes in 13C NMR spectra of intact hearts under conditions of varied metabolite enrichment.

Dynamic changes in 13C NMR signal from enriched glutamate pools within hearts have been examined under varied conditions of metabolite pool size and fractional enrichment. Relative signal intensities of 13C-enriched glutamate isotope isomers were similar within spectra from both intact hearts and corresponding in vitro samples. The parameters used to assess metabolic activity with 13C NMR proved independent of fractional enrichment and pool size. The data show the importance of acknowledging unlabeled, 13C NMR invisible metabolites.

Human insulin autoantibody fine specificity and H and L chain use.

Fine specificity and H and L chain isotypes of insulin autoantibodies in sera from 11 subjects were examined. None of these 11 subjects was treated with exogenous insulin. Two patterns of fine specificity were found. In one, the autoantibodies were specific for human insulin, with a requirement for threonine at B30. The conservative substitution in pork insulin (threonine to alanine) abrogated IgG binding by these sera. Insulin autoantibodies in other sera cross-reacted with beef, pork, and human insulin; not requiring threonine at B30. Reciprocal competitive inhibition experiments showed that epitopes recognized by the human specific insulin autoantibodies were exclusively on the B chain, whereas the cross-reactive sera contain autoantibodies that recognize both the B chain and combinatorial (A and B chain) epitopes. The fine specificity of cross-reactive insulin autoantibodies are thus similar to insulin antibodies from insulin-treated subjects. When IgG subclasses and L chains of insulin autoantibodies were examined, however, restricted C region usage was found. The hierarchy was IgG3 greater than G1 greater than G2 greater than G4; with one subclass dominant in each serum, although others were used. L chain use was similarly restricted. There was no correlation between isotype and fine specificity or between H and L chain type. It is concluded that heterogeneity of insulin autoantibodies is restricted. The response is probably more oligo- or pauciclonal than insulin antibody from insulin-treated subjects.

Factors affecting the insulin autoantibody ELISA.

IgG antibodies to insulin are present in insulin-treated patients and are detected in the prodrome of untreated type I diabetes. Sporadic reports of autoantibodies to insulin suggest that they are also present in other disorders. To establish the incidence of insulin autoantibodies in other endocrine and autoimmune diseases an ELISA was used to examine sera from 529 subjects with no prior insulin therapy. These untreated patients included: normal controls (adults and children), newly-diagnosed type I diabetes, first-degree relatives of diabetics, type II diabetes, Graves' hyperthyroidism, and systemic lupus erythematosus. As a positive control group, 280 insulin-treated patients were studied. Measurement of IgG antibodies by direct binding to insulin coated plates was complicated by differences between adult and pediatric populations and by overlap of binding between treated and untreated subjects. Competitive inhibition with excess soluble human insulin overcame these problems and permitted identification of insulin specific binding. Using this approach insulin antibodies were most frequent in insulin-treated diabetics (98%) and in type I diabetics (37%) prior to treatment. The absolute numbers of subjects with insulin autoantibody in the other groups differed depending upon whether a cut-off for binding (mean + 2SD of controls) or for insulin inhibition of binding (45%) was used. Regardless of the criteria used there were subjects (2-24%) in all groups tested with circulating insulin-specific IgG autoantibody detected by ELISA. These low level antibodies detected in solid phase assays may be part of the normal immune repertoire.

Inhibition of protein synthesis in loblolly pine hypocotyls by mannitol-induced water stress.

The relationship between mannitol-induced water stress and protein synthesis was investigated in hypocotyl slices of loblolly pine (Pinus taeda L.). Mannitol-induced water stress inhibited the incorporation of L-[(35)S]methionine into protein. As the water potential decreased, incorporation of label into protein decreased in both the soluble- and membrane-protein fractions. There were no significant differences in response to water stress among seed sources from four different geographical regions.

Host acceptance and discrimination byComperia merceti (Compere) (Hymenoptera: Encyrtidae) and evidence for an optimal density range for resource utilization.

The cement used by females ofSupella longipala (F.) (Orthoptera∶Blattellidae) to bind their oothecae to substrates acts as a kairomone for host acceptance by the parasitoidComperia merceti. C. merceti discriminates parasitized from unparasitized oothecae and oviposts at reduced levels in the former. Low survival rates for parasitoids reared from oothecae receiving fewer than four ovipositions suggests that an "optimal density range" for resource utilization byC. merceti exists.