Ischemic stress induces deposition of amyloid β immunoreactivity in human brain

The histoblot immunostaining technique for locating and characterizing amyloidogenic proteins was used to obtain information about the relationship of cerebral ischemia/hypoxia to the accumulation of amyloid protein (Aß). We investigated brains of 131 subjects (ages 25–94 years, mean 72 years). Three distribution patterns of A immunoreactivity were identified: (1) colocalization with diffuse and neuritic plaques of Alzheimer's disease (AD) and aging; (2) diffuse punctate deposits in the cerebral cortex in association with small vessel cerebral vascular disease; and (3) cerebral cortical accumulation localized to arterial boundary zones and other regions susceptible to ischemic/hypoxic injury designated stress-induced deposits (SID). SID were not identified in tissue sections by immunohistochemical, Congo red or Bielschowsky silver techniques; no histological abnormalities were present in adjacent formalin-fixed tissue sections. SID occurred in subjects with histories of cerebral ischemia, and severe orthostatic hypotension. There was also an association with aging in general and with the incidence of neuritic plaques specifically. These latter findings are consistent with the hypothesis that brain ischemia/hypoxia plays a role in the pathogenesis of AD.     

Cohort profile: biological pathways of risk and resilience in Syrian refugee children (BIOPATH)

The BIOPATH cohort was established to explore the interplay of psychosocial and biological factors in the development of resilience and mental health problems in Syrian refugee children. Based in Lebanon, a middle-income country significantly impacted by the refugee crisis, it is the first such cohort of refugees in the Middle East. Families were recruited from informal tented settlements in the Beqaa region using purposive cluster sampling. At baseline (October 2017–January 2018), N = 3188 individuals participated [n = 1594 child–caregiver dyads; child gender, 52.6% female; mean (SD) age = 11.44 (2.44) years, range = 6–19]. Re-participation rate at 1-year follow-up was 62.8%. Individual interviews were conducted with children and primary caregivers and biological samples collected from children. Measures include: (1) children’s well-being and mental health problems (using tools validated against clinical interviews in a subsample of the cohort); (2) psychosocial risk and protective factors at the level of the individual (e.g. coping strategies), family (e.g. parent–child relationship), community (e.g. collective efficacy), and wider context (e.g. services); (3) saliva samples for genetic and epigenetic (methylation) analyses; (4) hair samples to measure cortisol, dehydroepiandrosterone (DHEA) and testosterone. This cohort profile provides details about sampling and recruitment, data collection and measures, demographic data, attrition and potential bias, key findings on resilience and mental health problems in children and strengths and limitations of the cohort. Researchers interested in accessing data should contact Professor Michael Pluess at Queen Mary University of London, UK (e-mail: m.pluess@qmul.ac.uk).

     

Differential susceptibility to rearing experience: the case of childcare

Background:  Inconsistencies regarding developmental effects of non-maternal childcare may be caused by neglecting the possibility that children are differentially susceptible towards such experiences.
Method:  Interactions between difficult/negative child temperament and childcare type, quantity, and quality on teacher-rated behavior problems and social competence at 54 months and in kindergarten were investigated via multiple regression using data from the NICHD Study of Early Child Care.
Results:  Childcare quality interacted with infant negativity in predicting behavior problems and social competence, whereas effects of quantity and type were independent of child temperament. Consistent with Belsky's (1997) differential susceptibility hypothesis, children with difficult temperaments as infants exhibited both more behavior problems when faced with low quality care and fewer when experiencing high quality care than children with easy temperaments.
Conclusions:  Negatively-emotional infants appear to be more affected by the quality of care they experience – both negatively and positively – than other young children.     

Optimal use of L-asparaginase (NSC-109229) in acute lymphocytic leukemia

Between 1971 and 1974, 646 evaluable patients under 20 years of age with previously untreated acute lymphocytic leukemia were treated according to Cancer and Leukemia Group B (formerly Acute Leukemia Group B) Protocol 7111. On a random basis, they received a 10-day course of 1,000 units/kg/day of L-asparaginase before, during, or after a 3-week course of vincristine and corticosteroid. A control group received vincristine and corticosteroid for 4 weeks but no asparaginase. The overall complete remission rate was 85%, which was not altered significantly by any of the induction variables. Patients who received asparaginase for 10 days subsequent to vincristine and corticosteroid had a significantly longer complete remission duration with an estimated median of 45 months, compared to 20 months for the group receiving no asparaginase and 27 months for the other 2 asparaginase regimens. The beneficial effect of asparaginase was noted, irrespective of which 1 of the 2 intensification and maintenance programs the patients received. The 5-year projection indicates a complete remission rate of 50% for those patients receiving subsequent asparaginase as compared to 41% of those induced on other regimens in this study and thus is superior to the use of only vincristine and corticosteroid.     

Vantage sensitivity: a framework for individual differences in response to psychological intervention

Purpose

People differ significantly in their response to psychological intervention, with some benefitting more from treatment than others. According to the recently proposed theoretical framework of vantage sensitivity, some of this variability may be due to individual differences in environmental sensitivity, the inherent ability to register, and process external stimuli. In this paper, we apply the vantage sensitivity framework to the field of psychiatry and clinical psychology, proposing that some people are more responsive to the positive effects of psychological intervention due to heightened sensitivity.

Methods

After presenting theoretical frameworks related to environmental sensitivity, we review a selection of recent studies reporting individual differences in the positive response to psychological intervention.

Results

A growing number of studies report that some people benefit more from psychological intervention than others as a function of genetic, physiological, and psychological characteristics. These studies support the vantage sensitivity proposition that treatment response is influenced by factors associated with heightened sensitivity to environmental influences. More recently, studies have also shown that sensitivity can be measured with a short questionnaire which appears to predict the response to psychological intervention.

Conclusions

Vantage sensitivity is a framework with significant relevance for our understanding of widely observed heterogeneity in treatment response. It suggests that variability in response to treatment is partly influenced by people’s differing capacity for environmental sensitivity, which can be measured with a short questionnaire. Application of the vantage sensitivity framework to psychiatry and clinical psychology may improve our knowledge regarding when, how, and for whom interventions work.

     

Maternal trait anxiety, emotional distress, and salivary cortisol in pregnancy

Animal models suggest that stress-induced hormonal changes in the mother during pregnancy lead to enduring changes in the fetus and empirical links between prenatal maternal stress and negative child development have been discerned repeatedly in human studies. But the role of heritable personality traits has received little attention in the latter work. The goal of the current study was to investigate the relationship between maternal personality, psychological measures of maternal distress and maternal salivary cortisol during pregnancy. Maternal reports of personality (16 PF) and stress-related psychological measures (depression, pregnancy-related anxiety, perceived stress, negative life events) as well as salivary cortisol samples of 66 healthy pregnant women were collected in early and late pregnancy. Maternal trait anxiety proved related to all stress-related psychological measures and high anxiety predicted low baseline cortisol awakening levels in early pregnancy. Maternal trait anxiety is related to both psychological and biological stress measures during pregnancy.     

Vincristine, prednisone and L-asparaginase in the induction of remission in children with acute lymphoblastic leukemia following relapse.

Two hundred and twenty-seven children with recurrent acute lymphoblastic leukemia were treated with various combinations of vincristine, prednisone, cyclophosphamide and L-asparaginase in an approach to the induction of remission. The combination of L-asparaginase 1,000 mu/kg iv q.d. x 10, vincristine 2.0 mg/m2iv q.w. x 4 and prednisone 40 mg/m2 p.o.q.d. x 28 days was found to be highly effective. The incidence of remission was 73%. No significant improvement was achieved when cyclophosphamide was added to this regimen. Various combinations of cytosine arabinoside, cyclophosphamide, vincristine, prednisone, BCNU or CCNU failed to maintain remission duration for more than two or three months. Neither BCNU nor CCNU prevented the development of CNS leukemia.     

Characterization of eighteen novel microsatellite markers and multiplex PCR protocol for Fagus sylvatica

Eighteen novel microsatellite markers for European Beech, Fagus sylvatica, were developed using next-generation sequencing technique. Subsequently, four multiplex PCRs were established for the fast and cost-effective use of the primers. In 60 individuals, we found 3–12 alleles per locus, an expected and observed heterozygosity of 0.445–0.821 and 0.250–0.867, respectively. Fixation index was significant in three loci. Yet, if these measures were jointly estimated with the probability of null alleles, these loci and an additional two indicated low occurrence of null alleles while the overall fixation index was non-significant. The loci were not in linkage disequilibrium. Overall, these markers will be useful for population genetic research to support management decisions for the preservation of this species in changing environmental conditions.