The co-creation, initial piloting, and protocol for a cluster randomised controlled trial of a coach-led positive body image intervention for girls in sport.

BACKGROUND: Globally, girls disengage from sports at an earlier age and higher rate than boys. This is, in part, due to the unique body image challenges that girls face, relative to their male peers. Existing intervention efforts that aim to reduce girls' negative body image and movement experiences have proven marginally effective, if not ineffective. This paper outlines the co-creation, initial piloting and protocol for a cluster randomised controlled trial of Body Confident Athletes (BCA); an in-person, coach-led intervention that aims to foster positive body image and sports enjoyment among girls. METHODS: Following co-creation and an initial pilot, a two-armed cluster randomised controlled trial will assess the immediate (post-intervention) and short-term (1-month and 3-month follow-up) impact of BCA on girls' (N = 1,036; 11-17 years old) body image, sports enjoyment, and affect. Sport organisations will be randomly allocated (1:1) into either an intervention or waitlist control condition. Girls and coaches in the intervention condition will complete three 60-minute sessions over three consecutive weeks. The primary outcome will be the immediate change in girls' body esteem, with secondary outcomes assessing the immediate and short-term changes in girls' body appreciation, self-objectification, attuned self-care, sports enjoyment, and affect. DISCUSSION: This research is the first to utilise an international multi-stakeholder partnership to co-create and evaluate an intervention that addresses the intersection of girls' body image and sport experiences. The theoretical and methodological considerations of this research have led to a feasible intervention and trial protocol, and if proven effective, BCA may assist in reducing the global gender disparity in sports participation. TRIAL REGISTRATION NUMBER: NCT05594524 , registered 25th October 2022.

Improving body image at scale among Brazilian adolescents: study protocol for the co-creation and randomised trial evaluation of a chatbot intervention.

BACKGROUND: Body image concerns are prevalent among Brazilian adolescents and can lead to poor psychological and physical health. Yet, there is a scarcity of culturally-appropriate, evidence-based interventions that have been evaluated and made widely available. Chatbot technology (i.e., software that mimics written or spoken human speech) offers an innovative method to increase the scalability of mental health interventions for adolescents. The present protocol outlines the co-creation and evaluation of a body image chatbot for Brazilian adolescents via a partnership between academics, industry organisations and the United Nations Children's Fund (UNICEF). METHODS: A two-armed fully remote randomised controlled trial will evaluate the chatbot's effectiveness at improving body image and well-being. Adolescent girls and boys (N = 2800) aged 13-18 years recruited online will be randomly allocated (1:1) into either: 1) a body image chatbot or 2) an assessment-only control condition. Adolescents will engage with the chatbot over a 72-hour period on Facebook Messenger. Primary outcomes will assess the immediate and short-term impact of the chatbot on state- and trait-based body image, respectively. Secondary outcomes will include state- and trait-based affect, trait self-efficacy and treatment adherence. DISCUSSION: This research is the first to develop an evidence-informed body image chatbot for Brazilian adolescents, with the proposed efficacy trial aiming to provide support for accessible, scalable and cost-effective interventions that address disparities in body image prevalence and readily available resources. TRIAL REGISTRATION NUMBER: NCT04825184 , registered 30th March 2021.

The role of the RAS pathway in iAMP21-ALL.

Intrachromosomal amplification of chromosome 21 (iAMP21) identifies a high-risk subtype of acute lymphoblastic leukaemia (ALL), requiring intensive treatment to reduce their relapse risk. Improved understanding of the genomic landscape of iAMP21-ALL will ascertain whether these patients may benefit from targeted therapy. We performed whole-exome sequencing of eight iAMP21-ALL samples. The mutation rate was dramatically disparate between cases (average 24.9, range 5-51) and a large number of novel variants were identified, including frequent mutation of the RAS/MEK/ERK pathway. Targeted sequencing of a larger cohort revealed that 60% (25/42) of diagnostic iAMP21-ALL samples harboured 42 distinct RAS pathway mutations. High sequencing coverage demonstrated heterogeneity in the form of multiple RAS pathway mutations within the same sample and diverse variant allele frequencies (VAFs) (2-52%), similar to other subtypes of ALL. Constitutive RAS pathway activation was observed in iAMP21 samples that harboured mutations in the predominant clone (⩾35% VAF). Viable iAMP21 cells from primary xenografts showed reduced viability in response to the MEK1/2 inhibitor, selumetinib, in vitro. As clonal (⩾35% VAF) mutations were detected in 26% (11/42) of iAMP21-ALL, this evidence of response to RAS pathway inhibitors may offer the possibility to introduce targeted therapy to improve therapeutic efficacy in these high-risk patients.

The clinical impact of thiopurine methyltransferase polymorphisms on thiopurine treatment.

Acute lymphoblastic leukaemia (ALL) is the most common malignancy of childhood. Although current treatment results in long term survival in over 70% of cases there is evidence that as many as 50% could have been cured using a less complex regimen with a lower incidence of long term side effects. In previous studies it has been found that thiopurines given as part of continuing therapy are key agents in preventing relapse. However, optimal administration during continuing therapy is often not achieved. Variation in the level of thiopurine methyltransferase (TPMT) activity appears to be a major molecular determinant of the extent of thiopurine metabolism. TPMT activity shows a trimodal distribution pattern. A lack of activity is found in approximately one in 300 Caucasians; approximately 11% have intermediate activity and the remaining 89% high activity. Congenital loss of activity is associated with grossly elevated levels of active drug and profound myelosuppression on exposure to thiopurines. This loss of activity has been attributed to single nucleotide polymorphisms (SNPs) within the TPMT gene. The frequency of SNPs is related to ethnicity, with the most common in Caucasians being TPMT*3A which is characterized by a G to A transition at position 460 with a substitution of alanine for tyrosine at amino acid 154 (A154Y) and a transition of A to G at nucleotide 719 resulting in a change of tyrosine to cysteine at position 240 (Y240C). Polymorphisms have also been identified within the 5' flanking promoter region of the TPMT gene due to a variable number of tandem repeats (VNTR*3-*8). An overview of the polymorphisms identified to date, their implication on the metabolism of the thiopurine drugs and therapeutic importance will be discussed.

Allergy history does not predict skin test reactivity in asthmatic children.

We prospectively assessed how well patient report of allergy to cat, dust mite, and grass predicted the results of skin prick testing to those allergens in 95 asthmatic children. Children between 4 and 18 years old with physician-documented asthma provided a detailed standardized allergy history and then underwent skin prick testing. The children were categorized by asthma severity. The diagnostic accuracy, which was the primary outcome measure, as well as sensitivity, specificity, and positive and negative predicted values were calculated for allergy history with regards to skin test reactivity. The diagnostic accuracy of allergy history in identifying skin test reactivity was 65%, 50%, and 56% for cat, dust mite, and grass, respectively. Asthma severity did not affect the diagnostic accuracy. Allergy history was a poor predictor of skin test reactivity in this group of asthmatic children.

An examination of the role of clinical psychology in meeting the needs of young disabled clients and their families/carers.

This paper examines the views of clients with a physical disability, general practitioners and staff working in health and social work physical disability services about the needs of young disabled people. The most common area of disability seen by GPs was respiratory, followed by cardiac problems and stroke. With the exception of cardiac patients a third to over half of GPs felt that the needs of the identified groups were not being adequately met, in particular the needs of individuals with progressive neuromuscular problems. Over a quarter of clients felt that their needs were not being adequately met. Ninety-five percent of GPs and 100% of staff identified psychological needs of clients. For clients themselves, physical needs are ranked highest, with over 33 percent identifying psychological problems, 50 percent neuropsychological problems and 25 percent psychosexual difficulties as priority needs. In relation to carers, over 90 percent of GPs, 100% of staff and 50 percent of clients highlighted psychological needs. The majority of participants felt that clinical psychology had an important role to play in physical disability services. There was broad agreement on the areas of need which psychology would be seen to address. These were psychological needs, behavioural problems, neuropsychological problems and relationship/psychosexual difficulties. A high percentage of both staff and GPs also saw a role for clinical psychology in meeting the psychological, relationship and psychosexual needs of carers.

Professional composition of community learning disability teams in Scotland: implications for service provision.

A survey of all trusts in Scotland who provided specialist services to people with learning disabilities was made with a response rate of 100%. An examination was made of the professional composition of the community learning disability teams and the population covered. A disparity was found across Scottish trusts in the professions represented in the community learning disability teams with some professions having no input. Nursing and Clinical Psychology were found to be the two professional groups with largest representation across Scotland and along with Speech and Language Therapy had representation in all of the Teams. A review of some of the factors which have impacted on the role and professional composition of these services is made and the implications discussed.

Expression of DNA mismatch repair proteins in acute lymphoblastic leukaemia and normal bone marrow.

Errors during normal DNA synthesis may produce mismatched base pairs. 6-Mercaptopurine (6MP), given during continuing therapy in acute lymphoblastic leukaemia (ALL), undergoes intracellular activation to give cytotoxic thioguanine nucleotides which are then incorporated into the DNA of dividing cells in place of guanine. Cell death is thought to result from futile attempts at mismatch repair. Previous work has shown that cell lines with a defect in this pathway develop tolerance to incorporated 6-thioguanine bases. In order to investigate the possible relevance of mismatch repair to the chemosensitivty of blasts to 6MP, relative to normal tissues, we have measured the expression of the mismatch repair proteins MLH1, MSH2, PMS2 and MSH6 in blasts from children and adults with ALL and in normal bone marrows, using western blotting. Fifty cases of childhood ALL, 22 cases of adult ALL and 7 normal marrows have been studied. Expression of MSH2, and of MLH1 in all but three cases, was detectable in all the blasts studied. Noticeably, expression of MLH1 was not detected in any of the normal marrow samples. MSH2 was detected in 4 of the normal marrows. Expression of PMS2 was not detected in 29 cases of ALL and, like MLH1, was absent from each of the normal marrow samples. In contrast, MSH6 was detected in all of the normal marrows and all but 16 of the cases of ALL. There was no difference in expression between adults and children. These results may help to explain the relative sensitivity of leukaemic blasts to thiopurines at presentation as compared to normal bone marrow.

Health status of pediatric refugees in Portland, ME.

BACKGROUND: An understanding of the health conditions affecting pediatric refugees is essential to providing responsible health care for them when they arrive in the United States. OBJECTIVE: To assess the health status of pediatric refugees in an area of increased refugee resettlement. DESIGN: Retrospective medical records review. SETTING: Ambulatory clinic at Maine Medical Center in Portland, a community and referral hospital. PATIENTS: One hundred thirty-two refugees and immigrants aged 2 months through 18 years who had initial health care evaluations during 1994 and 1995. RESULTS: Sixty-six patients arrived from Africa, 22 from the former Yugoslavia, and the remainder from the former Soviet Union, Middle Asia, Southeast Asia, and Latin America. The mean age of the patients was 10 years; 56 (42.4%) were female. The overall health status of most of the children was good, with most having appropriate weight and height for age. Dental caries and dermatologic conditions were the most prevalent findings on physical examination. Two patients had evidence of traumatic injuries. The results of tuberculin (Mantoux) tests were positive (> or =10 mm) in 45 (35.2%) of 128 children for whom results were noted, hepatitis B surface antigen was detected in 5 (4.0%) of 124 children, and hepatitis B surface antibody was detected in 26 (21.1%) of 123 children. Five (16.7%) of 30 children younger than 6 years had elevated blood lead levels; anemia was detected in 25 (19.7%) of 127 children with hematocrit results available. Stool specimens were obtained from 87 patients, of whom 38 (43.7%) had pathogenic parasites in at least 1 specimen. CONCLUSIONS: Pediatric refugees arrive in the United States with a variety of conditions that may be unfamiliar to practitioners trained in this country. The results of this study support the screening of refugees from Africa and other regions for tuberculosis, stool parasites, and hepatitis B.

The challenges of early discharge. Common newborn problems in the first few weeks of life.

In a thorough discussion of a published series on early discharge, Britton, Britton and Beebe note that methodological limitations, study design problems and heterogeneity sorely limit the conclusions that may be drawn from published studies about early discharge. These authors found that the 1980 recommendations of the AAP about early discharge are still appropriate. They recommend individualizing the discharge decision based on mother-infant health, as well as on psychosocial and socioeconomic factors. These authors apparently seek to temper the headlong rush to early discharge with an awareness of the wider societal context within which childbirth must be understood. Although the literature paints a positive picture of early home discharge, existing research still lacks the statistical power and scientific evidence to support this practice. There are many positive reasons for the early discharge of a mother-infant dyad, but they may have nothing to do with monetary savings. As with many things we do in our clinical practice, there is much room for the input of nurse practitioners, not only in providing care, but also in the shaping of health care policy.

Visual determinants of the leftward cradling bias: a preliminary report.

A dominant leftward cradling bias is typically found in women in non-feeding interactions with infants. The present study investigated Manning and Chamberlain's (1991) claim that the perception of an infant, or doll, in the left visual field was critical for the establishment of this cradling preference. A leftward bias, of similar magnitude to that shown in previous studies, was shown in a sample of undergraduate female students when their left eye was not occluded, and in imagery. Unexpectedly, the cradling bias was not significantly affected by left eye occlusion. Paradoxically, a group of males, who showed no clear lateral bias, were strongly affected by eye occlusion. A strong leftward cradling bias was also found in the blind. These data do not support the suggestion (Manning & Chamberlain, 1991) that visual information is a primary determinant of the leftward cradling bias.

Sensitivity of testis tumour cells to chemotherapeutic drugs: role of detoxifying pathways.

In contrast to most other types of cancer, metastatic testicular germ cell tumours (TGCT) are cured in most patients using cisplatin-based combination chemotherapy. The biochemical mechanisms underlying this sensitivity have not been defined. Drug detoxification can modulate response to chemotherapy in vivo and in vitro, and therefore we measured levels of glutathione (GSH), glutathione-S-transferase (GST) and both constitutive and cisplatin- and dexamethasone-induced levels of metallothionein (MT) in five human testis tumour cell lines. The levels were compared with those in five human bladder cancer cell lines and two cell lines with cisplatin resistance acquired in vitro. GSH levels were relatively low in the testis tumour cell lines, as might be expected in drug-sensitive cells, and there was a 77-fold increase in GSH levels in the cisplatin-resistant testis tumour cell line. GST levels were similar in the two cell types, while metallothionein levels were relatively high in the testis tumour cell lines. These data indicate that GSH may contribute to the sensitivity of TGCT to chemotherapy, and that GSH expression may be involved in the acquisition of cisplatin resistance in these tumours.

Corticosteroid resistance is increased in lymphoblasts from adults compared with children: preliminary results of in vitro drug sensitivity study in adults with acute lymphoblastic leukaemia.

The prognosis of acute lymphoblastic leukaemia (ALL) in adults is poor compared with children in terms of complete remission (CR) and leukaemia-free survival. In children in vitro resistance of leukaemic cells to various cytotoxic agents is an independent poor prognostic marker, but the relevance of in vitro drug resistance in adults to poor prognosis has not been described. Lymphoblasts from 16 adults and 32 children with ALL at initial presentation were assayed for in vitro drug sensitivity in a short-term culture system using the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as an indicator of cell viability. The following drugs were tested: prednisolone, daunorubicin, mitozantrone, etoposide, melphalan and 6-thioguanine. At initial presentation, lymphoblasts from adults demonstrated a significantly higher degree of in vitro resistance to prednisolone than those from children (P < 0.01). Glucocorticoid resistance may be a fundamental difference between adult and childhood ALL which may underlie different biological aspects and also explain the difference in prognosis. Lymphoblasts from adults who achieved CR were more sensitive in vitro to prednisolone (P = 0.07), daunorubicin (P < 0.05), mitozantrone (P < 0.01) and melphalan (P < 0.05) than cells from those who did not. The MTT assay can predict response to induction chemotherapy in adults and therefore discriminate between standard- and high-risk patients. The assay, however, is not suitable for selection of the most effective agent for treatment because of in vitro cross-resistance of lymphoblasts to various drugs tested.

Purification of an alpha class glutathione S-transferase from melphalan-resistant Chinese hamster ovary cells and demonstration of its ability to catalyze melphalan-glutathione adduct formation.

We have shown previously that a Chinese hamster ovary cell line (designated CHO-Chlr), generated by exposure to chlorambucil and demonstrating a greater than 20-fold collateral resistance to melphalan, showed increased expression of an alpha form of glutathione S-transferase (GST) associated with amplification of GST genes. Here, we demonstrate that GST purified from CHO-Chlr cells contains a form with a pI of 9, not present in CHO-K1 cells or Chinese hamster liver, which has the ability to accelerate the formation of glutathione-melphalan adducts. This result provides evidence that overexpression of the alpha class GST may be directly responsible for the development of resistance to bifunctional alkylating agents.

Plasma creatine kinase isoenzymes in the Bar harbor dystrophic mouse.

Increased activity of the MM isoenzyme of creatine kinase (CK) was found in plasma from Bar Harbor dystrophic mice of the 129/ReJ dy/dy strain when compared to the findings in non-dystrophic controls. Total plasma CK activity was only slightly increased in dystrophic animals but plasma from both normal and dystrophic mice showed large amounts of the BB isoenzyme of creatine kinase. This isoenzyme was also found to be present in mouse platelets. It is concluded that BB isoenzyme from platelets could have obscured the contribution of muscle CK to the total plasma CK activity and the CK isoenzyme quantitation is needed to evaluate muscle disorders in rodents.