Pain and learning in primary school: a population-based study.

Despite the frequency of pain among children, little is known about its effects on learning and school outcomes. The objective of this study was to quantify the association of pain and academic achievement while taking into account the presence of co-occurring emotional symptoms. A population-based stratified random sample of 1239 students aged 8 to 9 years from primary schools in Melbourne, Australia, was recruited for the Childhood to Adolescence Transition Study. Children indicated sites of pain that had lasted for a day or longer in the past month using a pain manikin. Depressive- and anxiety-related symptoms were assessed using child-reported items. National assessment results for reading and numeracy were used to measure academic achievement. Sixty-five percent of children reported pain in at least 1 body site and 16% reported chronic pain. Increasing number of pain sites was associated with poorer reading scores in a dose-response fashion (β = -3.1; 95% confidence interval -4.9 to -1.3; P < 0.001). The association was only partly attenuated when adjusting for emotional symptoms (β = -2.6; 95% confidence interval -4.5 to -0.8; P < 0.001) and was not moderated by emotional symptoms. Children with chronic pain were a year behind their peers in both reading and numeracy. Among primary school students, pain was associated with lower reading scores even after adjusting for the presence of emotional symptoms. Although population-based longitudinal studies will be required to ascertain consistency and possible causality, grounds exist for considering pain and emotional symptoms in the assessment of children with reading difficulties

Self-harm in primary school-aged children: Prospective cohort study

Introduction No prospective studies have examined the prevalence, antecedents or concurrent characteristics associated with self-harm in non-treatment-seeking primary school-aged children. Methods In this cohort study from Melbourne, Australia we assessed 1239 children annually from age 8–9 years (wave 1) to 11–12 years (wave 4) on a range of health, social, educational and family measures. Past-year self-harm was assessed at wave 4. We estimated the prevalence of self-harm and used multivariable logistic regression to examine associations with concurrent and antecedent factors. Results 28 participants (3% of the 1059 with self-harm data; 18 girls [3%], 10 boys [2%]) reported self-harm at age 11–12 years. Antecedent (waves 1–3) predictors of self-harm were: persistent symptoms of depression (sex-age-socioeconomic status adjusted odds ratio [aOR]: 7.8; 95% confidence intervals [CI] 2.6 to 24) or anxiety (aOR: 5.1; 95%CI 2.1 to 12), frequent bullying victimisation (aOR: 24.6; 95%CI 3.8 to 158), and recent alcohol consumption (aOR: 2.9; 95%CI 1.2 to 7.1). Concurrent (wave 4) associations with self-harm were: having few friends (aOR: 8.7; 95%CI 3.2 to 24), poor emotional control (aOR: 4.2; 95%CI 1.9 to 9.6), antisocial behaviour (theft—aOR: 3.1; 95%CI 1.2 to 7.9; carrying a weapon—aOR: 6.9; 95%CI 3.1 to 15), and being in mid-puberty (aOR: 6.5; 95%CI 1.5 to 28) or late/post-puberty (aOR: 14.4; 95%CI 2.9 to 70)

Anti-Transforming Growth Factor ß Antibody Treatment Rescues Bone Loss and Prevents Breast Cancer Metastasis to Bone

Breast cancer often metastasizes to bone causing osteolytic bone resorption which releases active TGFβ. Because TGFβ favors progression of breast cancer metastasis to bone, we hypothesized that treatment using anti-TGFβ antibody may reduce tumor burden and rescue tumor-associated bone loss in metastatic breast cancer. In this study we have tested the efficacy of an anti-TGFβ antibody 1D11 preventing breast cancer bone metastasis. We have used two preclinical breast cancer bone metastasis models, in which either human breast cancer cells or murine mammary tumor cells were injected in host mice via left cardiac ventricle. Using several in vivo, in vitro and ex vivo assays, we have demonstrated that anti-TGFβ antibody treatment have significantly reduced tumor burden in the bone along with a statistically significant threefold reduction in osteolytic lesion number and tenfold reduction in osteolytic lesion area. A decrease in osteoclast numbers (p = 0.027) in vivo and osteoclastogenesis ex vivo were also observed. Most importantly, in tumor-bearing mice, anti-TGFβ treatment resulted in a twofold increase in bone volume (p<0.01). In addition, treatment with anti-TGFβ antibody increased the mineral-to-collagen ratio in vivo, a reflection of improved tissue level properties. Moreover, anti-TGFβ antibody directly increased mineralized matrix formation in calverial osteoblast (p = 0.005), suggesting a direct beneficial role of anti-TGFβ antibody treatment on osteoblasts. Data presented here demonstrate that anti-TGFβ treatment may offer a novel therapeutic option for tumor-induced bone disease and has the dual potential for simultaneously decreasing tumor burden and rescue bone loss in breast cancer to bone metastases. This approach of intervention has the potential to reduce skeletal related events (SREs) in breast cancer survivors

Parents' views on care of their very premature babies in neonatal intensive care units: a qualitative study

Background The admission of a very premature infant to the neonatal intensive care unit (NICU) is often a difficult time for parents. This paper explores parents’ views and experiences of the care for their very premature baby on NICU. Methods Parents were eligible if they had a baby born before 32 weeks gestation and cared for in a NICU, and spoke English well. 32 mothers and 7 fathers were interviewed to explore their experiences of preterm birth. Although parents’ evaluation of care in the NICU was not the aim of these interviews, all parents spoke spontaneously and at length on this topic. Results were analysed using thematic analysis. Results Overall, parents were satisfied with the care on the neonatal unit. Three major themes determining satisfaction with neonatal care emerged: 1) parents’ involvement; including looking after their own baby, the challenges of expressing breast milk, and easy access to their baby; 2) staff competence and efficiency; including communication, experience and confidence, information and explanation; and 3) interpersonal relationships with staff; including sensitive and emotional support, reassurance and encouragement, feeling like an individual. Conclusions Determinants of positive experiences of care were generally consistent with previous research. Specifically, provision of information, support for parents and increasing their involvement in the care of their baby were highlighted by parents as important in their experience of care

Therapeutic targets for bone metastases in breast cancer

Breast cancer is prone to metastasize to bone. Once metastatic cells are in the bone marrow, they do not, on their own, destroy bone. Instead, they alter the functions of bone-resorbing (osteoclasts) and bone-forming cells (osteoblasts), resulting in skeletal complications that cause pathological fractures and pain. In this review, we describe promising molecular bone-targeted therapies that have arisen from recent advances in our understanding of the pathogenesis of breast cancer bone metastases. These therapies target osteoclasts (receptor activator of nuclear factor kB ligand, integrin αvβ3, c-Src, cathepsin K), osteoblasts (dickkopf-1, activin A, endothelin A) and the bone marrow microenvironment (transforming growth factor β, bone morphogenetic proteins, chemokine CXCL-12 and its receptor CXCR4). The clinical exploitation of these bone-targeted agents will provide oncologists with novel therapeutic strategies for the treatment of skeletal lesions in breast cancer

Melanism in Peromyscus Is Caused by Independent Mutations in Agouti

Identifying the molecular basis of phenotypes that have evolved independently can provide insight into the ways genetic and developmental constraints influence the maintenance of phenotypic diversity. Melanic (darkly pigmented) phenotypes in mammals provide a potent system in which to study the genetic basis of naturally occurring mutant phenotypes because melanism occurs in many mammals, and the mammalian pigmentation pathway is well understood. Spontaneous alleles of a few key pigmentation loci are known to cause melanism in domestic or laboratory populations of mammals, but in natural populations, mutations at one gene, the melanocortin-1 receptor (Mc1r), have been implicated in the vast majority of cases, possibly due to its minimal pleiotropic effects. To investigate whether mutations in this or other genes cause melanism in the wild, we investigated the genetic basis of melanism in the rodent genus Peromyscus, in which melanic mice have been reported in several populations. We focused on two genes known to cause melanism in other taxa, Mc1r and its antagonist, the agouti signaling protein (Agouti). While variation in the Mc1r coding region does not correlate with melanism in any population, in a New Hampshire population, we find that a 125-kb deletion, which includes the upstream regulatory region and exons 1 and 2 of Agouti, results in a loss of Agouti expression and is perfectly associated with melanic color. In a second population from Alaska, we find that a premature stop codon in exon 3 of Agouti is associated with a similar melanic phenotype. These results show that melanism has evolved independently in these populations through mutations in the same gene, and suggest that melanism produced by mutations in genes other than Mc1r may be more common than previously thought

Evolution of sex-specific pace-of-life syndromes: genetic architecture and physiological mechanisms

Sex differences in life history, physiology, and behavior are nearly ubiquitous across taxa, owing to sex-specific selection that arises from different reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis predicts that most variation in such traits among individuals, populations, and species falls along a slow-fast pace-of-life continuum. As a result of their different reproductive roles and environment, the sexes also commonly differ in pace-of-life, with important consequences for the evolution of POLS. Here, we outline mechanisms for how males and females can evolve differences in POLS traits and in how such traits can covary differently despite constraints resulting from a shared genome. We review the current knowledge of the genetic basis of POLS traits and suggest candidate genes and pathways for future studies. Pleiotropic effects may govern many of the genetic correlations, but little is still known about the mechanisms involved in trade-offs between current and future reproduction and their integration with behavioral variation. We highlight the importance of metabolic and hormonal pathways in mediating sex differences in POLS traits; however, there is still a shortage of studies that test for sex specificity in molecular effects and their evolutionary causes. Considering whether and how sexual dimorphism evolves in POLS traits provides a more holistic framework to understand how behavioral variation is integrated with life histories and physiology, and we call for studies that focus on examining the sex-specific genetic architecture of this integration