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Aims: The optimal echocardiographic predictors of cardiovascular outcome in heart failure (HF) with preserved ejection fraction (HFpEF) are unknown. We aimed to identify independent echocardiographic predictors of cardiovascular outcome in patients with HFpEF. Methods and results: Systematic literature search of three electronic databases was conducted from date of inception until November 2022. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for echocardiographic variables from multivariate prediction models for the composite primary endpoint of cardiovascular death and HF hospitalization were pooled using a random effects meta‐analysis. Specific subgroup analyses were conducted for studies that enrolled patients with acute versus chronic HF, and for those studies that included E/e′, pulmonary artery systolic pressure (PASP), renal function, natriuretic peptides and diuretic use in multivariate models. Forty‐six studies totalling 20 056 patients with HFpEF were included. Three echocardiographic parameters emerged as independent predictors in all subgroup analyses: decreased left ventricular (LV) global longitudinal strain (HR 1.24, 95% CI 1.10–1.39 per 5% decrease), decreased left atrial (LA) reservoir strain (HR 1.30, 95% CI 1.13–1.1.50 per 5% decrease) and lower tricuspid annular plane systolic excursion (TAPSE) to PASP ratio (HR 1.17, 95% CI 1.07–1.25 per 0.1 unit decrease). Other independent echocardiographic predictors of the primary endpoint were a higher E/e′, moderate to severe tricuspid regurgitation, LV mass index and LA ejection fraction, although these variables were less robust. Conclusions: Impaired LV global longitudinal strain, lower LA reservoir strain and lower TAPSE/PASP ratio predict cardiovascular death and HF hospitalization in HFpEF and are independent of filling pressures, clinical characteristics and natriuretic peptides. These echocardiographic parameters reflect key functional changes in HFpEF, and should be incorporated in future prospective risk prediction models. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to assess the prevalence and the burden of difficult‐to‐treat primary ITP (pITP), defined by the need for another ITP treatment after romiplostim and eltrombopag. Adult patients were selected in the prospective, real‐world CARMEN‐France registry up to December 2021. Out of 821 adult patients with pITP, 29 had difficult‐to‐treat ITP (3.5%; 95% confidence interval [CI]: 2.3%–4.8% in total; 7.6%; 95% CI: 4.9%–10.2% of patients needing ≥2nd line treatment). The 3‐year cumulative incidence of bleeding, infection and thrombosis was 100%, 24.1% and 13.8% respectively. The median cumulative duration of hospital stays was 31 days (median follow‐up: 30.3 months). [ABSTRACT FROM AUTHOR]

Aim: The incidence of anaphylaxis is increasing globally in tandem with changing environmental and lifestyle factors. There is very limited data on very early childhood presentations. We aim to assess changes in rates, characteristics and management of infant anaphylaxis in a paediatric ED over a 15‐year period. Methods: We conducted a retrospective study of children <2 years of age who presented with verified anaphylaxis comparing cases in years 2003–2007 with those in 2013–2017. Standardised information was collected on demographics, clinical presentation, management and triggers. Results: Manually confirmed anaphylaxis rates in <2 year olds increased from 3.6 to 6.2 per 104 population (OR 1.7, 95% CI: 1.3–2.7; p < 0.001) with the greatest increase in <1 year olds. Anaphylaxis severity increased between 2003–2007 and 2013–2017 (OR 2.3, 95% CI: 1.2–4.3; p = 0.018). Failure to administer adrenaline was reduced in 2013–2017 (p = 0.007). Food was the leading anaphylaxis trigger (97.85%). Conclusion: This is the first study to suggest an increase in the incidence and severity of ED anaphylaxis presentations in children aged <2 years. Increased awareness of specific characteristics in this age group is required to facilitate timely recognition and optimal management. Further large‐scale studies are warranted to understand underlying environmental drivers and find prevention strategies to reduce the burden of disease. [ABSTRACT FROM AUTHOR]

While protein medications are promising for treatment of cancer and autoimmune diseases, challenges persist in terms of development and injection stability of high‐concentration formulations. Here, the extensional flow properties of protein‐excipient solutions are examined via dripping‐onto‐substrate extensional rheology, using a model ovalbumin (OVA) protein and biocompatible excipients polysorbate 20 (PS20) and 80 (PS80). Despite similar PS structures, differences in extensional flow are observed based on PS identity in two regimes: at moderate total concentrations where surface tension differences drive changes in extensional flow behavior, and at small PS:OVA ratios, which impact the onset of weakly elastic flow behavior. Undesirable elasticity is observed in ultra‐concentrated formulations, independent of PS identity; higher PS contents are required to observe these effects than in analogous polymeric excipient solutions. These studies reveal novel extensional flow behaviors in protein‐excipient solutions, and provide a straightforward methodology for assessing the extensional flow stability of new protein‐excipient formulations. [ABSTRACT FROM AUTHOR]

Black youth face marginalization at multiple levels, which can have deleterious developmental consequences. An important focus is the misrepresentation of Black emotional expression at the intersection of structural racism and clinical psychology. As efforts to incorporate anti‐racism in psychological care continue, there is a need to increase specificity to improve clinical efforts. The white hegemony for both boys and girls leads to the dehumanization of Black teens, which often leads to misdiagnosis and incomplete treatment plans. [ABSTRACT FROM AUTHOR]

Aim: Penicillin allergy accounts for the majority of all reported adverse drug reactions in adults and children. Foregoing first‐line antibiotic therapy due to penicillin allergy label is associated with an increased prevalence of infections by resistant organisms and longer hospitalisation. Clinician awareness of allergy assessment, referral indications, management of allergy and anaphylaxis is therefore vital but globally lacking. We aim to assess the knowledge of penicillin allergy, assessment and management in Western Australian health professionals. Methods: An anonymous survey was distributed to pharmacists, nurses and physicians within Western Australian paediatric and adult Hospitals, Community and General Practice. Results: In total, 487/611 were completed and included in the statistical analysis. Only 62% (301/487) of respondents routinely assessed for patient medication allergies. Of those who assessed allergy, 9% (28/301) of respondents met the Australian standards for allergy assessment. Only 22% (106/487) of participants correctly cited all indications for management with adrenaline in anaphylaxis to antibiotics and 67% (197/292) of physicians rarely or never referred to an allergy service. Paediatric clinicians had an increased understanding of allergy assessment and anaphylaxis management. Recent penicillin allergy education within a 5‐year period led to significant improvements in allergy knowledge. Conclusion: Overall, knowledge, assessment and management of penicillin allergies among practitioners in Western Australia are currently inadequate in adults and paediatric clinicians to provide safe and effective clinical care. The implementation of a targeted education program for WA health professionals is urgently required and is expected to improve clinician knowledge and aid standardised penicillin assessment (de‐labelling) practices. [ABSTRACT FROM AUTHOR]

Aims: A better knowledge of opioid prescribing patterns would help to identify areas of potential improvement in cancer pain management. This study aimed to identify potential inappropriate use (PIU) of strong opioid analgesics in cancer outpatients in their last year of life. Methods: A retrospective cohort of cancer patients who died between 2011 and 2014 and were exposed as outpatient to a strong opioid analgesic in the last year of life was identified in the Echantillon Généraliste de Bénéficiaires (a 1/97th random sample of the French general population). Prescribing patterns of strong opioids were analysed and PIU was defined by at least 1 of these criteria: overlapping prescriptions; contraindicated prescriptions; lack of laxatives; potential drug interactions; prescription in patients hospitalized for opioid‐related disorders. Factors associated with PIU were investigated through a multiple logistic regression model. Results: One third of the 2236 patients (median age 72 years [interquartile range: 61–82], 44.1% women) presented a PIU (insufficient laxative prescription [19.6% of patients], insufficient background treatment with transmucosal fentanyl [14.8%], overlapping prescriptions [2.6%]). The rate of PIU significantly decreased from 37.6% (2011) to 29.8% (2014). For patients with a duration of opioid use ≥3 months, factors associated with PIU were fentanyl prescription (adjusted odds ratio = 2.36; 95% confidence interval [1.86–3.00]) and previous use of strong opioid (adjusted odds ratio = 1.88; [1.50–2.36]). Conclusion: In France, 1/3 of cancer patients exposed to strong opioids experienced PIU and this proportion tended to decrease over time. There is still room for progress in cancer pain management at the end of life. [ABSTRACT FROM AUTHOR]

Objectives: A quality improvement approach was used to increase pediatric liver transplant recipient live and inactive vaccination rates by assessing titers and recommending vaccinations. Methods: A new screening and immunization process for both live and inactive vaccines was discussed with families at their annual visit. Antibody titers for varicella, measles, mumps, rubella, Haemophilus influenzae type B, hepatitis A, and hepatitis B were obtained. Specific criteria were developed for live virus vaccination candidacy. Vaccines were recommended based on patient titers and vaccination candidacy criteria. Surveillance for adverse effects to live vaccines was performed. Repeat titers were obtained approximately 1‐month post‐vaccine administration. Results: After PDSA cycle 1, 99% (71/72) of pediatric liver transplant patients had titers obtained. Live vaccines were recommended for 32 patients and 16 (50%) were vaccinated. Inactive vaccines were recommended to 64 patients, and 31 (48%) were vaccinated. Eight of 13 (62%) patients with follow‐up titers achieved immunity for inactive vaccines. Zero patients had an adverse reaction to any live vaccine. Ten of 12 (83%) patients with follow‐up titers achieved immunity from live vaccines. The most common barriers to receive live vaccines included not scheduling appointment with primary care provider (n = 3) and "non‐vaccinators" (n = 3). Conclusions: Administering live and inactive vaccines to select pediatric liver transplant patients appears to be safe and effective in our studied population. For PDSA cycle 2, we will continue our current practice and consider offering vaccines in transplant clinic, since this was a barrier to vaccination identified during PDSA cycle 1. [ABSTRACT FROM AUTHOR]

Aim: To determine advantages conferred by a youth‐specific transition clinic model for young adults with type 1 diabetes (T1D) at Westmead Hospital (WH) as compared with Australian registry data. Methods: Prospectively collected data included age, diabetes duration, visit frequency, post code, BMI, mode of insulin delivery, continuous glucose monitoring, HbA1c, albumin creatinine ratio, BP, retinopathy and diabetic ketoacidosis (DKA) for all WH T1D clinic attendees aged 16–25 between January 2017 and June 2018 (n = 269). Results were compared with data collected during the same time period from 2 separate Australian data registries, one longitudinal (Australasian Diabetes Data Network, ADDN) and one a spot survey (the Australian National Diabetes Audit, ANDA). Results: Across the three cohorts, HbA1c was similar (respectively, WH, ADDN, ANDA; 8.7%[72mmol/mol], 8.7%[72mmol/mol], 8.5%[69mmol/mol]) and HbA1c was significantly higher in young adults <21 years (8.7–8.9%[73‐75mmol/mol]) as compared with ≥21 years (8.5%[69mmol/mol], p <.002). In the WH cohort, median interval between visits was shorter than in ADDN (4.5 vs. 9.0 months) and DKA was lower (respectively, 3.6 and 9.2/100 patient years; p <.001). Conclusions: While suboptimal HbA1c was recorded in all centres, the WH model of care saw increased attendance and reduced admissions with DKA as compared with other Australian adult centres. A model of care for young people with type I diabetes as they transition to adult care was benchmarked with two separate Australian data registries. Similar glycaemic outcomes were achieved nationally but the care model achieved a marked reduction in diabetic ketoacidosis and increased clinic attendance frequency. [ABSTRACT FROM AUTHOR]

In our patient's case, her rash began 7 days after commencement of the suspected culprit drug, phenobarbitone which is consistent with early-onset DRESS syndrome.4 Drugs most implicated are antiepileptics (50%), including phenobarbitone (11.5%). GLO:81V/01nov22:jpc16078-fig-0002.jpg PHOTO (COLOR): 2 Patient's drug hypersensitivity timeline. gl She was advised to avoid phenobarbitone and vancomycin lifelong and to avoid amoxicillin, amoxicillin/clavulanic acid, trimethoprim and sulfonamides until further drug patch testing. Early accurate diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) can be challenging in patients with a rash on multiple new medications with an associated viral infection. [Extracted from the article]

Background: Low vitamin D levels have been associated with allergic diseases. Vitamin D has potent immunomodulatory properties, but the mechanisms remain unclear. We have investigated the effect of oral vitamin D supplementation on circulating immune cell phenotypes in infants. Method: A double‐blinded randomised controlled trial was conducted to investigate the effect of oral vitamin D supplementation (400 IU/d) on eczema and immune development. A subset of 78 infants was included in this analysis. Phenotypic analysis of immune cell subsets was performed using flow cytometry. Results: Vitamin D supplementation resulted in median 25(OH)D levels of 80.5 vs 59.5 nmol/L in the placebo group at 3 months of age (P =.002) and 87.5 vs 77 nmol/L at 6 months of age (P =.08). We observed significant changes in immune cell composition from birth (cord blood) to 6 months of age. Vitamin D supplementation did not impact these changes, nor did immune cell composition correlate with plasma 25(OH)D levels. Through exploratory analysis, we identified possible associations with eczema development and increased abundance of naïve CD4‐ T cells at birth, as well as associations with basophils, iNKT and central memory CD4+ T cells, and altered expression patterns of IgE receptor (FcεR1) on monocytes and dendritic cells with eczema at 6 months. Conclusions: Vitamin D supplementation in infants who were vitamin D sufficient at birth did not affect developmental changes in immune cells during the first 6 months of life. However, immune cell profiles at birth and at 6 months of age were associated with early life eczema. [ABSTRACT FROM AUTHOR]

Background: Drug‐induced immunosuppression is necessary to prevent rejection of the foreign organ in transplanted patients, but neoplastic and virus‐associated skin diseases are frequent complications. Reflectance confocal microscopy (RCM) recently emerged as a promising tool for the early diagnosis of skin lesions. Materials and methods: A total of 61 skin lesions, among them 20 basal cell carcinomas, six Bowen's diseases, 23 actinic keratoses, and 12 verrucae, were analyzed. All lesions were clinically evaluated followed by RCM evaluation by two independent dermatologists and histological examination. Results: For the diagnosis of basal cell carcinoma, a sensitivity of 100% by both investigators (INV I + II) and a specificity of 100% by INV I and 80% by INV II were achieved. The sensitivity average rate for RCM features reached by both investigators ranged between 60% and 100%, and the specificity between 55% and 90%. For the diagnosis of actinic keratosis, a concordant sensitivity of 94.4% and a specificity of 80% (INV I) and 60% (INV II) were detected. The sensitivity average rate of specific RCM criteria ranged between 72.3% and 97.2%, whereas specificity ranged between 20% and 90%. Regarding verrucae, RCM confirmed the histological diagnosis with a sensitivity of 85.7% (INV I) and 100% (INV II), while specificity was 100% and 80%, respectively. Conclusion: Reflectance confocal microscopy resulted to be a reliable tool for the noninvasive diagnosis of neoplastic and virus‐associated skin changes in organ transplant recipients. Nevertheless, given the frequency and diagnostic complexity of the hyperkeratotic lesions occurring post‐transplantation, larger cohorts of patients are required to confirm and consolidate these findings. [ABSTRACT FROM AUTHOR]

Parents who experienced infertility have increasingly used medically assisted reproduction (MAR) to add children to their families over the past few decades. These parents will need to decide if they will tell their children about being conceived using MAR. Although MAR information sharing operates within family contexts, little is known about the role of conversation orientation—one family contextual factor—in child outcomes associated with MAR information sharing in middle childhood. Derived from the Family Communication Patterns Theory, this study proposes that conversation orientation moderates the associations between MAR information sharing and children's psychosocial adjustment. This proposal was tested using a sample of 81 6‐ to 12‐year‐old MAR‐conceived children from 55 families and a structured observational measure of conversation orientation. Multiple regression analyses showed that MAR information sharing interacted with conversation orientation to influence children's behavioral and attention problems but not emotional problems. In families with high conversation orientation, MAR information sharing was not significantly associated with children's behavioral and attention problems. In families with low conversation orientation, MAR information sharing was significantly associated with an increase in children's behavioral and attention problems. Results of this exploratory study demonstrate the potential significance of general communication orientation in understanding child outcomes of MAR information sharing and highlight the needed family context nuances in MAR research. [ABSTRACT FROM AUTHOR]

Growing use of in vitro fertilization (IVF) has resulted in an elevated twin birth rate, and a burgeoning population of IVF twins who are now aging into adolescence and beyond. This study tests a model examining whether parental conformity expectations have differential effects on twins' versus singletons' parent–adolescent relationship satisfaction, and if this effect is indirectly associated with relative changes in twins' and singletons' internalizing and externalizing behavior from middle childhood to adolescence. Using a sample of 278 IVF twins and singletons, path models demonstrate that twin status and conformity expectations interact to influence parent–adolescent relationships. Although there was an association between twin status and mother–adolescent relationship satisfaction among parents with high conformity expectations (r = .25, p < .01), this relationship was nonsignificant among parents with low conformity expectations (r = .05, p = .85). The differential effect of conformity expectations on parent–adolescent relationship satisfaction for twins and singletons was indirectly associated with relative changes in twins' and singletons' externalizing behavior from middle childhood to adolescence. Results demonstrate that higher levels of parental conformity expectations may not have the same effect on adolescent twins and singletons. [ABSTRACT FROM AUTHOR]

Atropinic drugs are known to potentially induce physical and/or mental impairments in the elderly. The aim of this study was to investigate trends of atropinic exposure in patients ≥65 years in France between 2006 and 2015. A repeated cross‐sectional study was performed quarterly from January 1, 2006 to December 31, 2015, in the 'Echantillon Généraliste des Bénéficiaires (EGB)', a representative sample of the French population. Exposed patients were identified using the Anticholinergic Durán's list. Outcomes were rate of patients exposed to at least one atropinic drug (atropinic prevalence rate) and atropinic burden per patient (sum of atropinic burden scores). Interrupted time series were used to analyze the impact of market withdrawal of some drugs with atropinic properties during the period of the study. The number of patients ≥65 years registered in the EGB ranged from 75 611 in 2006 to 95 389 in 2015. Atropinic prevalence rate decreased significantly from 45.6% in 2006 to 33.2% in 2015 (−12.4%, slope significance P < 0.05). Subjects aged ≥85 years were the most exposed. Total atropinic burden decreased significantly between 2006 and 2015 (2.2 ± 1.7 in 2006; 2.0 ± 1.5 in 2015; slope significance P < 0.05), especially in patients ≥85 years. Market withdrawals for safety reasons of some atropinic drugs were significantly associated with a decrease in the atropinic prevalence rate (P < 0.05) and atropinic burden per patient (P < 0.05). In conclusion, atropinic drug exposure in the elderly significantly decreased in France between 2006 and 2015. This decrease can be partly explained by regulatory measures against some atropinic drugs. [ABSTRACT FROM AUTHOR]

Aim: To determine if skin testing (ST) in addition to extended oral provocation challenge (OPC) is necessary for beta-lactam allergy verification in an Australian paediatric population.Methods: This was a retrospective study (176 children) that undertook assessments for beta-lactam allergy from 2006 to 2015 at a tertiary paediatric hospital. Patients either underwent direct OPC without ST or ST plus challenge if ST was negative.Results: The analysis included children with a history of varying rash types/severity as well as angioedema and reported anaphylaxis. A direct OPC was undertaken in 73 children. Three children reacted with one anaphylaxis. A total of 103 children underwent ST, with 13 children (12.6%) reacting. Of the 90 who subsequently proceeded to OPC, 4 reacted. A total of 132 children were given an extended oral course of the culprit antibiotic, to which 6 children reacted.Conclusions: A direct OPC with the culprit drug in Australian children can be safely performed, avoiding resource-intensive and painful ST. Our data demonstrate that a prior history of anaphylaxis does not necessarily predict IgE-mediated allergy, as detected by positive immediate ST or reactions to oral challenge. Such history should not detract from efforts to assess these children for antibiotic allergy. We suggest that extended courses of at least 5 days are important in paediatric antibiotic de-labelling as six children (4.5% of those who were prescribed the extended course) reacted in our study and even developed symptoms late in the extended course, from days 2 to 6. [ABSTRACT FROM AUTHOR]

Abstract: Conscientiousness is a personality trait associated with many important life outcomes, but little is known about the mechanisms that underlie it. We investigated its neural correlates using functional connectivity analysis in fMRI, which identifies brain regions that act in synchrony. We tested the hypothesis that a broad network resembling a combination of the salience and ventral attention networks, which we provisionally label the goal priority network (GPN), is a neural correlate of Conscientiousness. Self‐ and peer‐ratings of Conscientiousness were collected in a community sample of adults who underwent a resting‐state fMRI scan (N = 218). An independent components analysis yielded five components that overlapped substantially with the GPN. We examined synchrony within and between these GPN subcomponents. Synchrony within one of the components—mainly comprising regions of anterior insula, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex—was significantly associated with Conscientiousness. Connectivity between this component and the four other GPN components was also significantly associated with Conscientiousness. Our results support the hypothesis that variation in a network that enables prioritization of multiple goals may be central to Conscientiousness. [ABSTRACT FROM AUTHOR]

Abstract: Main goal of this study was to analyse how empowerment processes and bottom‐up activities aimed at healthier food choices and food environment could be initiated among a group of senior citizens (between 60 and 75 years old). The intervention was set up as a pilot study in a rural community (15,000 inhabitants) in the federal state of Bavaria, South Eastern Germany. A process evaluation documented how group formation and empowerment processes developed during the course of the intervention. Extensive field notes were taken in 27 meetings, interviews (n = 13) and focus groups (n = 4) were conducted with participants and key persons at different points of the intervention. Data were analysed using content analysis. The intervention succeeded in motivating senior citizens to participate in regular meetings over 11 months. During the intervention, the group members’ awareness of factors influencing their eating behaviour increased. Furthermore, they developed ideas to improve the community's food environment and accomplished duties needed to implement these ideas. However, initiating empowerment processes, especially in terms of fostering leadership and transferring responsibility, took longer than expected and could be realised only partially. The findings support a further use and evaluation of the empowerment approach for addressing nutritional aspects among senior citizens. [ABSTRACT FROM AUTHOR]

The article offers information on kawasaki disease.

The article discusses the case of an infant with persistent neutropenia caused by congenital cytomegalovirus (cCMV). Topics discussed include the antenatal history and symptoms of the patient, the management of cCMV infection with oral valganciclovir and granulocyte-colony stimulating factor (G-CSF) therapy, and the hearing and neurodevelopmental consequences of missed or delayed diagnosis of cCMV.

Increased medically assisted reproduction ( MAR) use to treat infertility has resulted in a growing twin birth rate. Little is known about parent-child relationships for twin relative to singleton children in middle childhood. This study fills this gap by examining parent-child relationships in 57 families with eighty 6- to 12-year-old MAR twin and singleton children using observational data (warm and supportive communication, control, and hostility). Nested ANCOVAs indicate that while mothers exhibit similar interactional behaviors toward twins and singletons, fathers have less optimum behaviors toward twins relative to singletons. Twins displayed less engaged behavior with mothers and fathers relative to singletons. Given the vitality of parent-child relationships for family and child adjustment, future studies should examine determinants and outcomes of twin-singleton relationship differences to bolster twins' and their families' functioning. [ABSTRACT FROM AUTHOR]

The dramatic rise in early childhood allergic diseases indicates the specific vulnerability of the immune system to early life environmental changes. Dietary changes are at the centre of lifestyle changes that underpin many modern inflammatory and metabolic diseases, and therefore are an essential element of prevention strategies. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also an interest in the early life effects of specific nutrients including polyunsaturated fatty acids, oligosaccharides (soluble fibre), antioxidants, folate and other vitamins that have documented effects on immune function as well as metabolism. A better understanding of nutritional programming of immune health, nutritional epigenetics and the biological processes sensitive to nutritional exposures in early life may lead to dietary strategies that provide more tolerogenic conditions during early immune programming and reduce the burden of many inflammatory diseases, not just allergy. [ABSTRACT FROM AUTHOR]

This article provides an overview of the methods, assumptions, and key findings of behavioral genetics methodology for family researchers with a limited background. We discuss how family researchers can utilize and contribute to the behavioral genetics field, particularly in terms of conducting research that seeks to explain shared environmental effects. This can be done, in part, by theoretically controlling for genetic confounds in research that seeks to determine cause-and-effect relationships among family variables and individual outcomes. Gene-environment correlation and interaction are especially promising areas for the family researcher to address. Given the methodological advancements in the field, we also briefly comment on new methods in molecular genetics for studying psychological mental health disorders. [ABSTRACT FROM AUTHOR]

Background Most animal models currently used to evaluate antinociceptive efficacy of analgesics rely on the assessment of evoked pain behaviours as primary endpoints. Mehtods Here, we have developed and characterized the carrageenaninduced locomotor activity impairment ( CLAIM) model to objectively assess non-evoked inflammatory pain behaviour in rats. In this model, 100 µL of 1% carrageenan was subcutaneously injected into the plantar aspect of the right hind paw and exploratory behaviour in the novel testing chamber was recorded using an automated locomotor activity system. Results Carrageenan-injected animals exhibited an exploratory behavioural deficit 2-7 h following injection compared to saline-injected animals. The severity of impairment was carrageenan dose related, and sensitive to the light intensity in the testing room. The effects of standard analgesics on CLAIM were examined 2 or 3 h following carrageenan injection. Diclofenac and ibuprofen, in a dose range exerting no effect on locomotor activity in naïve rats, exhibited dose-related reversal of CLAIM ( ED50 = 1.5 and 5.0 mg/kg, respectively), with comparable efficacy on carrageenan-induced thermal hyperalgesia ( ED50 = 2.0 and 6.0 mg/kg, respectively). Gabapentin and duloxetine produced no reversal of CLAIM, or attenuation of thermal hyperalgesia. Efficacy discrepancy was noted for morphine on thermal hyperalgesia and CLAIM. Additionally, amphetamine dose dependently reversed CLAIM, and similarly increased locomotor activity in normal animals. Discussion and Conclusion The results presented here demonstrate that CLAIM provides an objective assessment of non-evoked pain behaviours for acute inflammatory pain. The pharmacological profile of standard analgesics supports that CLAIM model can be used to identify agents to treat acute inflammatory pain in the clinic. [ABSTRACT FROM AUTHOR]

Previous research has demonstrated the protective effect of family and sibling closeness on child adjustment, but fewer studies have investigated how closeness is promoted within families. Guided by Family Communication Patterns Theory, we tested the association between family communication and sibling emotional and behavioral closeness, and whether adoptive status moderated this relationship. Participating families included 616 adoptive and nonadoptive families with two adolescent children. Hypotheses were tested using structural equation modeling. Sibling closeness was highest in families that emphasized both conversation and conformity and lowest in families that emphasized only conversation or neither conversation nor conformity. Emotional and behavioral closeness were differentially associated with adoption status, sibling age, and sibling gender. Few moderating effects of adoption status were found. Post hoc analyses showed moderating effects of sibling gender composition. [ABSTRACT FROM AUTHOR]

This study examined the relation between three variables related to adoptive family relationships (post-adoption contact between adoptive and birth family members, adoption communicative openness, and satisfaction with contact) and adoptee externalizing behavior in adolescence and emerging adulthood. The study included 190 families of infant-placed, domestic adoptees during childhood, adolescence, and emerging adulthood. Structural equation modeling (SEM) was used to analyze predictors of externalizing behavior from contact (adoptive parents and adolescent reports), adoption communicative openness (adoptive mothers), and satisfaction with contact (adoptive parents and adolescent). Externalizing behavior showed moderate stability across childhood, adolescence, and emerging adulthood. Contact and adoption communicative openness were related to each other, but not to externalizing behaviors in adolescence or emerging adulthood. Controlling for the effect of Childhood Externalizing, adoptive families most satisfied with contact reported relative declines in adoptee externalizing behavior during adolescence compared to those in less satisfied families. Satisfaction was also indirectly associated with Emerging Adult Externalizing, through its effect on Adolescent Externalizing. Although contact and adoption communicative openness were highly correlated with each other, neither was related to adoptees' externalizing behavior in adolescence or emerging adulthood. Family-level satisfaction with contact was more predictive of externalizing outcomes. [ABSTRACT FROM AUTHOR]

A recent meta-analysis revealed moderate shared environmental influences (C) on most forms of child and adolescent psychopathology (), including antisocial behavior. Critically, however, the research analyzed in this meta-analysis relied largely on specific informant-reports (and particularly parent and child reports), each of which is subject to various sources of rater bias. Observer-ratings of children's behaviors avoid many of these biases, and are thus well suited to verify the presence of C. Given this, we sought to buttress the evidence supporting C in two key ways. First, we sought to confirm that C contributes to observer-ratings in a sample of adoptive siblings, as similarity between adoptive siblings constitutes a 'direct' estimate of C. Second, we sought to confirm that these shared environmental influences persist across informants (i.e., the effects are not specific to the rater or the context in question). The current study examined the etiology of observer-ratings of acting-out behaviors, as well as sources of etiological overlap across observer-ratings, adolescent self-report and maternal-report in sample of over 600 biological and adoptive sibling pairs from the Sibling Interaction and Behavior Study (SIBS). Results revealed moderate and significant shared environmental influences on observer-ratings (31%), as well as on the other informant-reports (20-23%). Moreover, a portion of these effects overlapped across measures (C correlations ranged from .32 to .34). Such findings argue against passive gene-environment correlations (rGE) and rater bias as primary explanations for earlier findings of C on antisocial behavior, and in this way, offer a critical extension of prior work indicating that the role of shared environmental influences on child and adolescent antisocial behavior was dismissed too soon. [ABSTRACT FROM AUTHOR]

The article discusses a study that investigated morphological and cytoarchitectural changes of brain structures in methylazoxymethanol acetate (MAM)-exposed rats, with the use of in vivo volumetric magnetic resonance imaging (MRI), manganese-enhanced MRI, and diffusion tensor imaging (DTI), for the study of cerebral pathology of schizophrenia. MAM-exposed rats exhibited enlarged lateral and third ventricles and reduced hippocampal volumes, consistent with observations in schizophrenia.

Background Atopic sensitization to the house dust mite (HDM) is associated with altered antibody responses to the nasopharyngeal colonizing bacterium Haemophilus influenzae and children admitted to the emergency department for asthma exacerbation have reduced IgG responses to HDM allergens. Objective To investigate anti-bacterial and anti-allergen antibody responses during convalescence from asthma exacerbation and differences found in exacerbations associated with and without viral infection. Results IgE antibodies to the P6 bacterial antigen increased in 60% of sera during convalescence and for many children achieved titres as high as IgE titres to allergens. In contrast IgE anti-HDM titres declined during convalescence. The anti-bacterial IgE titres were the same in subjects with and without virus infection while the anti-HDM IgE declined more rapidly in virus-infected subjects. IgG titres to the major HDM allergens showed no consistent increase and the overall IgG anti-HDM titres even declined in subjects without a virus infection. Anti-bacterial IgG antibodies in contrast to IgE did not change. Patients with frequent episodic or persistent asthma had similar IgE anti-bacterial titres to patients with infrequent asthma during the acute phase, although they had reduced IgG titres to both the bacteria and the HDM. Conclusions During the period following an acute exacerbation of asthma there was a marked and specific increase in anti-bacterial IgE compared with a reduced IgE response to HDM. This provides further support for the concept of T-helper type 2 responses to bacterial antigens playing a role in asthma pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Adolescent suicidality is a serious problem among American youth. Common risk factors for adolescent suicidality include depression and conduct problems but there is little agreement on the best means to assess these factors. We compared multiple informants (mothers, fathers, the adolescent and a sibling) and multiple assessment techniques using a sample of more than 460 families. Assessment techniques included paper–pencil instruments, observer ratings, and diagnostic interviews. Suicidality was assessed concurrently and two years after the risk assessment. Adolescent-reported paper–pencil instruments and diagnostic interviews were strongly associated with concurrent and future suicidality. Parents'' report of adolescent feelings and behaviors were also useful. Observed behaviors were not useful in assessing suicidality risk factors. Clinical recommendations include utilizing paper–pencil and diagnostic adolescent risk factor assessment and focusing on emotions. [Copyright &y& Elsevier]

Suicidal ideation during adolescence is quite common. Longitudinal ideation patterns may predict adolescents at greatest risk of progressing to more serious suicidal behaviors. We enumerated suicidal ideation trajectory subgroups and estimated subgroup association with later suicidal plans and attempts using data collected across a 13-year period from 552 Caucasian adolescents. Three subgroups were found: non-ideators (no ideation), decreasers (ideation decreased), and increasers (ideation persisted or increased). Probability of planning a suicide was greatest among increasers (females: .54, males: 51, p < .01). Probability of attempting suicide was greatest among male decreasers (.36, p < .01) and female increasers (.25, p < .01). [ABSTRACT FROM AUTHOR]

Adoption and family communication both affect adolescent adjustment. We proposed that adoption status and family communication interact such that adopted adolescents in families with certain communication patterns are at greater risk for adjustment problems. We tested this hypothesis using a community-based sample of 384 adoptive and 208 nonadoptive families. Adolescents in these families were, on average, 16 years of age. The results supported our hypothesis. Adopted adolescents were at significantly greater risk for adjustment problems compared to nonadopted adolescents in families that emphasized conformity orientation without conversation orientation and in families that emphasized neither conformity nor conversation orientation. Adolescents in families emphasizing conversation orientation were at lower risk for adjustment problems, regardless of adoption status. [ABSTRACT FROM AUTHOR]

A-85380 [3-(2(s)-azetidinylmethoxy) pyridine] is a neuronal nicotinic acetylcholine receptor (nAChR) agonist that has been a useful tool in the investigation of the function of nAChRs in both preclinical and clinical studies. Amongst nAChR subtypes, A-85380 shows selectivity for the α4β2 vs. the α7 or α1β1δγ nAChRs. In functional in vitro cation flux assays, A-85380 is a potent and full agonist. A-85380 has a broad-spectrum analgesic profile with efficacy in acute, persistent, and neuropathic pain models. As demonstrated using selective nAChR antagonists or α4 antisense, the α4β2 nAChR mediates the analgesic effects of A-85380. Interestingly, the site of action depends upon the type of pain as antinociception is mediated by descending inhibition into the spinal cord whereas anti-allodynia in neuropathic pain is mediated at both central and peripheral sites. Radiolabelled forms of A-85380 have been developed and shown to be safe for use in vivo in humans. In clinical studies using positron and photon emission tomography, marked decreases in α4β2 nAChRs have been seen in patients with Parkinson's and Alzheimer's disease. Although not developed as a therapeutic agent, A-85380 has proven to be an important component in the development of novel nAChR ligands for the treatment of pain and other disorders. [ABSTRACT FROM AUTHOR]

Introduction: Typical and atypical atrial flutters (AFLs) and atrial tachycardias (ATs) have been reported in patients with prior surgical atrial fibrillation ablation. The underlying mechanisms for this group of atrial tachyarrhythmias have not been well characterized and the efficacy of catheter ablation in their treatment is unknown. Methods and Results: Twenty patients (6 females) with a surface ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation underwent 26 electrophysiology studies. Patients manifesting sustained, organized, and beat-by-beat reproducible atrial electrical activity underwent complete right and left atrial catheter mapping and catheter ablation. One patient had no inducible tachyarrhythmia, while 5 patients had nonmappable arrhythmias. Nineteen of the 31 potentially mappable atrial tachyarrhythmias were completely characterized in 14 patients. The underlying mechanisms were macro-reentrant left AFL (n = 9), focal left AT (n = 3), typical right AFL (n = 6), and atypical right AFL (n = 1). Of the 19 completely characterized atrial arrhythmias, catheter ablation was performed for 18, and the procedure was successful for 13 of these. After a mean follow-up of 15 ± 10 months, 15 of 20 patients (75%) were in sinus rhythm including 10 of 13 patients (77%) with AT/flutter ablation. Ten patients, including 6 following ablation, were maintaining sinus rhythm without antiarrhythmic medications. Conclusions: Patients with an ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation may have multiple tachycardia mechanisms with the right or left atrium as the site of origin. Many of these rhythms may resolve with further maturation of surgical atrial fibrillation ablation (SAFA) lesions or be treatable with antiarrhythmic medication. However, persistent tachyarrhythmias can often be treated successfully with catheter mapping and ablation. [ABSTRACT FROM AUTHOR]

Research using retrospective or cross-sectional data suggests that suicidal ideation rates peak during mid-adolescence. This study used a longitudinal, community sample of adolescents who reported suicidal ideation repeatedly over 7 years to examine suicidal ideation trends. We hypothesized that a mid-adolescence peak in ideation is limited to adolescents exposed to friends' or family members' suicidality. Ideation trends were compared across groups exposed and not exposed to others' suicidality and statistically assessed using growth curve analyses. Overall, ideation rates peaked at age 15 years. Group comparisons revealed that the peak was limited to adolescents whose parents reported suicidality. [ABSTRACT FROM AUTHOR]

ABSTRACT ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride salt] is a selective neuronal nicotinic receptor (NNR) modulator with cognitive enhancing properties in animal models of cognitive functioning. Amongst NNR subtypes, ABT-089 shows selectivity for the cytisine binding site on the α4β2 receptor subtype as compared to the α-bungarotoxin (α-BgT) binding sites on the α7 and α1β1δγ receptor subtypes. In functional in vitro electrophysiological and cation flux assays, ABT-089 displays differential activity including agonism, partial agonism and antagonism depending upon the NNR subtype and assay. ABT-089 is as potent and efficacious as (-)-nicotine at evoking acetylcholine (ACh) release from hippocampal synaptosomes. Furthermore, ABT-089 is neuroprotective against excitotoxic glutamate insults, with even greater potency seen after chronic treatment. Similarly, ABT-089 is effective in models of cognitive functioning, including enhancement of baseline functioning as well as improvement of impaired cognitive functioning seen following septal lesioning and natural aging. In neuroprotective assays the compound is most potent by chronic administration. In stark contrast to the positive effects in the cognitive models, ABT-089 shows little propensity to induce adverse [ABSTRACT FROM AUTHOR]

In response to the recent economic crisis in Korea and its negative effects on families, the current study examined the interrelationships among economic pressure, emotional distress, marital conflict, and marital satisfaction for 236 Korean couples. The family stress model (Conger & Elder, 1994; Conger, Rueter, & Conger, 2000; Conger, Rueter, & Elder, 1999) was tested using structural equation modeling. The results generally supported the theoretical model, showing that economic pressure negatively affects marital satisfaction via emotional distress and marital conflict. The results also implied cultural differences in the process of family stress. Korean husbands' emotional distress did not affect marital conflict or marital satisfaction, suggesting that Korean husbands may differ from their wives in their reaction to emotional distress from economic pressure. [ABSTRACT FROM AUTHOR]

The article presents information on a study that tests a theory, which suggests that the level of parent-adolescent conflict is determined by family context. This theory was tested using structural equation modeling of data collected from 335 families over a 4-year period time, from the target children's early adolescence into their middle adolescence. According to this theory, a family atmosphere of warmth and supportiveness promotes successful negotiation of disagreements between parents and adolescent children and thereby helps to keep conflict at low to moderate levels. Under hostile, coercive conditions, however, parents and adolescents will be unlikely to resolve disagreements and conflict will escalate to dysfunctional levels. Findings of this study support the theory and it demonstrates the progressive nature of the proposed family process. Also, difficulties in hostile and coercive families appeared to worsen throughout early to middle adolescence, while parent-adolescent relationships in warm, supportive families tended to improve.

Three clones of marine Synechococcus (WH6501, WH7803, and WH8018) were grown through at least three transfers, at 6-day intervals, in synthetic medium with total iron concentrations from 10[SUP-9]to10[SUP-6]M. After 6 days of exponential growth, these cultures were harvested, and the cell density and protein and pigment concentrations were measured. Aliquots of the culture were assayed for their carbon fixation rates at two light intensities. Cell density and protein concentration increased by up to 7.8 times over a range of iron from the lowest (10[SUP-9]M) to the highest concentrations (10[SUP-6] M). The concentration of chlorophyll-a and phycobiliproteins showed a wider range of response, increasing by up to 48 times. The carbon fixation rate (per mL of culture) also increased approximately 40 times over the total range of iron concentration. The ranges of these biochemical and physiological responses were much lower than the range of total available iron, which was 1000-fold, and the range of total cellular iron, which was estimated to be about 160-fold. This "less-than-linear" relationship indicates that the cells are adapting to make more efficient use of iron under limiting conditions. Our results demonstrate characteristics of iron-limited Synechococcus that may be important in understanding the relationships between primary productivity and iron availability in the oceans. [ABSTRACT FROM AUTHOR]