Parkinson's disease-associated mutations in α-synuclein alters its lipid-bound state.

Lipid-binding properties of α-synuclein play a central role in protein aggregation and progression of Parkinson's disease (PD). α-Synuclein, an intrinsically disordered protein, binds to lipid membranes through the formation of two amphipathic helices that insert into the lipid bilayer. All disease-associated single point mutations have been identified to be within these helical regions of α-synuclein: V15A, A30P, E46K, H50Q, G51D, A53T, and A53V. However, the effects of these mutations on the bound states of the two α helices of the protein have yet to be fully characterized. In this report, we use a tryptophan fluorescence assay to measure the binding of the α helices of these PD-associated mutants to lipid membranes within the lipid-depletion regime. We characterize the binding behavior of each helix, revealing that, generally, the PD-associated mutants shift the equilibrium bound state away from the N-terminal helix of the protein toward helix 2 at lower lipid concentrations. Altogether, our results indicate that disruption to the equilibrium binding of the two α helices of α-synuclein could play a role in PD progression.

Binding equations for the lipid composition dependence of peripheral membrane-binding proteins.

The specific recognition of peripheral membrane-binding proteins for their target membranes is mediated by a complex constellation of various lipid contacts. Despite the inherent complexities of the heterogeneous protein-membrane interface, the binding dependence of such proteins is, surprisingly, often reliably described by simple models such as the Langmuir Adsorption Isotherm or the Hill equation. However, these models were not developed to describe associations with two-dimensional, highly concentrated heterogeneous ligands such as lipid membranes. In particular, these models fail to capture the dependence on the lipid composition, a significant determinant of binding that distinguishes target from non-target membranes. In this work, we present a model that describes the dependence of peripheral proteins on lipid composition through an analytic expression for their association. The resulting membrane-binding equation retains the features of these simple models but completely describes the binding dependence on multiple relevant variables in addition to the lipid composition, such as protein and vesicle concentration. Implicit in this lipid composition dependence is a new form of membrane-based cooperativity that significantly differs from traditional solution-based cooperativity. We introduce the Membrane-Hill number as a measure of this cooperativity and describe its unique properties. We illustrate the utility and interpretational power of our model by analyzing previously published data on two peripheral proteins that associate with phosphatidylserine-containing membranes: The transmembrane immunoglobulin and mucin domain-containing protein 3 (TIM3) that employs calcium in its association, and milk fat globulin epidermal growth factor VIII (MFG-E8) which is completely insensitive to calcium. We also provide binding equations for systems that exhibit more complexity in their membrane-binding.

Correction: The hallmarks of childhood abuse and neglect: A systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0243639.].

Social isolation-induced transcriptomic changes in mouse hippocampus impact the synapse and show convergence with human genetic risk for neurodevelopmental phenotypes.

Early life stress (ELS) can impact brain development and is a risk factor for neurodevelopmental disorders such as schizophrenia. Post-weaning social isolation (SI) is used to model ELS in animals, using isolation stress to disrupt a normal developmental trajectory. We aimed to investigate how SI affects the expression of genes in mouse hippocampus and to investigate how these changes related to the genetic basis of neurodevelopmental phenotypes. BL/6J mice were exposed to post-weaning SI (PD21-25) or treated as group-housed controls (n = 7-8 per group). RNA sequencing was performed on tissue samples from the hippocampus of adult male and female mice. Four hundred and 1,215 differentially-expressed genes (DEGs) at a false discovery rate of < 0.05 were detected between SI and control samples for males and females respectively. DEGS for both males and females were significantly overrepresented in gene ontologies related to synaptic structure and function, especially the post-synapse. DEGs were enriched for common variant (SNP) heritability in humans that contributes to risk of neuropsychiatric disorders (schizophrenia, bipolar disorder) and to cognitive function. DEGs were also enriched for genes harbouring rare de novo variants that contribute to autism spectrum disorder and other developmental disorders. Finally, cell type analysis revealed populations of hippocampal astrocytes that were enriched for DEGs, indicating effects in these cell types as well as neurons. Overall, these data suggest a convergence between genes dysregulated by the SI stressor in the mouse and genes associated with neurodevelopmental disorders and cognitive phenotypes in humans.

MFG-E8: a model of multiple binding modes associated with ps-binding proteins.

Membrane-binding proteins often associate with lipid membranes through a singular binding interface which is generally modeled as a two-state system: bound or unbound. However, even a single interface can engage with more than one mode of binding since a variety of interactions can contribute to the binding event. Unfortunately, the ability to clearly delineate the different binding modes of a singular binding interface has been elusive with existing models. Here, we present a study on milk fat globule EGF factor 8 (MFG-E8), which belongs to a class of proteins that identifies and binds phosphatidylserine (PS). These proteins detect membrane dysregulation implicated in exposed PS in apoptosis and malignant cells. In order to elucidate the factors affecting the binding of MFG-E8, we used a model system consisting of a series of lipid vesicles with varying PS mole fraction to identify the sensitivity of MFG-E8's binding affinity to changes in electrostatics using a tryptophan fluorescence spectral shift assay. Using a newly developed model, we experimentally identified three binding modes, each associated with a different number of PS lipids, with its cooperativity for binding being enhanced by the availability of negatively charged lipids. X-ray reflectivity experiments additionally suggest that MFG-E8's binding modes are influenced by membrane packing. The protocols established for elucidating MFG-E8's interaction with lipid membranes under different membrane conditions can be applied to the study of other membrane-binding proteins that target specific membrane attributes, such as fluidity and electrostatics, and help elucidate these membrane targeting mechanisms and their subsequent binding events.

Players' and parents' perceptions of injury in elite Northern Irish schools' rugby - A qualitative study.

OBJECTIVES: To explore schools' rugby players' and their parents' perceptions of injury. DESIGN: A qualitative study using focus groups. SETTING: Schools who compete in the Ulster Schools' Cup competition. PARTICIPANTS: 13 players and 9 parents. OUTCOME MEASURES: A thematic analysis approach was used to examine players' and parents' beliefs and attitudes towards injury, return to play and injury risk. RESULTS: Findings suggest schools' rugby players and their parents are aware of injury risk in the schoolboy game. They are aware of concussion injury but are less aware of musculoskeletal injury. Parents' perceptions of injury are based on their experience of their sons' injuries. Parents are unaware of return to play strategies for musculoskeletal injury. CONCLUSIONS: Schools' rugby players and their parents are aware of injury to some extent, however players' and parents' knowledge and understanding of injury is based on and informed by personal experience, not the evidence base. Whist they are aware of injury, many players will seek to push their fears to the back of their mind. However, for those players who have suffered severe injury, they are concerned about the risk of reinjury.

Academic, clinical and personal experiences of undergraduate healthcare students during the COVID-19 pandemic: A prospective cohort study.

BACKGROUND: Coronavirus disease 2019 has impacted upon the role and safety of healthcare workers, with the potential to have a lasting effect on their wellbeing. Limited research has been conducted during previous pandemics exploring how student healthcare workers are impacted as they study and train for their professional careers. OBJECTIVE: The aim of the current study was to examine the specific impact of COVID-19 on the academic, clinical and personal experiences of healthcare students. METHOD: Undergraduate students across three year groups within the School of Health Sciences at Ulster University completed online Qualtrics surveys at three timepoints during one academic year (2020/2021). Quantitative survey data was downloaded from Qualtrics into SPSS Version 25 for descriptive analysis of each cross-sectional sample. Qualitative survey data was downloaded into text format, which was thematically analysed using content analysis. RESULTS: 412 students completed the survey at Time 1 (October 2020), n = 309 at Time 2 (December 2020) and n = 259 at Time 3 (April 2021). Academically, the pandemic had mostly a negative impact on the learning environment, the development of practical skills, the assessment process and opportunities for peer learning and support. Students reported increased stress and challenges managing their workload and maintaining a sense of motivation and routine. Clinically, they felt unprepared by the university for placement where the pandemic had an increasingly negative impact over time on learning and skill development. In terms of personal experiences, despite the majority of students taking steps to keep physically and mentally well, negative impacts on friendships, mental wellbeing and concerns for family were reported. The pandemic had not impacted upon career choice for most students. CONCLUSION: Consideration must be given to the development of practical skills so students feel prepared for their professional careers given the practical nature of their roles. Programme coordinators should adopt a holistic approach to student wellbeing.

An investigation of coaches' awareness of injury in elite adolescent rugby union in Northern Irish schools - A qualitative study.

OBJECTIVES: To examine the decision-making processes employed by schools' Rugby coaches in the management of injured players and to explore the factors that influenced those decisions. A secondary objective was to gauge interest in an education focused toolkit for schools' Rugby coaches. DESIGN: A qualitative study using one-to-one online interviews. SETTING: Schools who compete in the Ulster Schools' Cup Rugby competition. PARTICIPANTS: Eleven Rugby union coaches from four post primary schools. OUTCOME MEASURES: A thematic analysis approach was used to examine the factors that influence schools' Rugby coaches' decision-making processes in the management of injured players. RESULTS: Findings suggest coaches are influenced in their decision making by four primary factors: their experience and learning, their relationships with other stakeholders, their knowledge and understanding of the roles and responsibilities of medical staff, healthcare and health fitness professionals, and resources available to them. CONCLUSIONS: Schools' Rugby coaches play a significant role in the supervision of injured adolescent Rugby players, often drawing from their playing and coaching experiences. Schools retain, or recommend the services, of healthcare professionals (HCPs) and health and fitness professionals (HFPs). The role of these healthcare and health and fitness professionals, along with their qualifications and experience is not fully understood by coaches. Coaches acknowledge that there is a need for further training and would welcome education initiatives aimed at increasing awareness of musculoskeletal injury in schoolboy Rugby players.

Rating the Quality of Smartphone Apps Related to Shoulder Pain: Systematic Search and Evaluation Using the Mobile App Rating Scale.

BACKGROUND: The successful rehabilitation of musculoskeletal pain requires more than medical input alone. Conservative treatment, including physiotherapy and exercise therapy, can be an effective way of decreasing pain associated with musculoskeletal pain. However, face-to-face appointments are currently not feasible. New mobile technologies, such as mobile health technologies in the form of an app for smartphones, can be a solution to this problem. In many cases, these apps are not backed by scientific literature. Therefore, it is important that they are reviewed and quality assessed. OBJECTIVE: The aim is to evaluate and measure the quality of apps related to shoulder pain by using the Mobile App Rating Scale. METHODS: This study included 25 free and paid apps-8 from the Apple Store and 17 from the Google Play Store. A total of 5 reviewers were involved in the evaluation process. A descriptive analysis of the Mobile App Rating Scale results provided a general overview of the quality of the apps. RESULTS: Overall, app quality was generally low, with an average star rating of 1.97 out of 5. The best scores were in the "Functionality" and "Aesthetics" sections, and apps were scored poorer in the "Engagement" and "Information" sections. The apps were also rated poorly in the "Subjective Quality" section. CONCLUSIONS: In general, the apps were well built technically and were aesthetically pleasing. However, the apps failed to provide quality information to users, which resulted in a lack of engagement. Most of the apps were not backed by scientific literature (24/25, 96%), and those that contained scientific references were vastly out-of-date. Future apps would need to address these concerns while taking simple measures to ensure quality control.

An Investigation Into the Use of mHealth in Musculoskeletal Physiotherapy: Scoping Review.

BACKGROUND: Musculoskeletal physiotherapy provides conservative management for a range of conditions. Currently, there is a lack of engagement with exercise programs because of the lack of supervision and low self-efficacy. The use of mobile health (mHealth) interventions could be a possible solution to this problem, helping promote self-management at home. However, there is little evidence for musculoskeletal physiotherapy on the most effective forms of mHealth. OBJECTIVE: The aim of this review is to investigate the literature focusing on the use of mHealth in musculoskeletal physiotherapy and summarize the evidence. METHODS: A scoping review of 6 peer-reviewed databases was conducted in March 2021. No date limits were applied, and only articles written in the English language were selected. A reviewer screened all the articles, followed by 2 additional researchers screening a random sample before data extraction. RESULTS: Of the 1393 studies, 28 (2.01%) were identified. Intervention characteristics comprised stretching and strengthening exercises, primarily for degenerative joint pain and spinal conditions (5/28, 18%). The most reported use of mHealth included telephone and videoconferencing calls to provide a home exercise program or being used as an adjunct to physiotherapy musculoskeletal assessment (14/28, 50%). Although patient satisfaction with mHealth was reported to be high, reasons for disengagement included a lack of high-quality information and poor internet speeds. Barriers to clinical uptake included insufficient training with the intervention and a lack of time to become familiar. CONCLUSIONS: mHealth has some benefits regarding treatment adherence and can potentially be as effective as normal physiotherapy care while being more cost-effective. The current use of mHealth is most effective when ongoing feedback from a health care professional is available.

Antipsychotics preserve telomere length in peripheral blood mononuclear cells after acute oxidative stress injury.

Antipsychotics may prolong or retain telomere length, affect mitochondrial function, and then affect the metabolism of nerve cells. To validate the hypothesis that antipsychotics can prolong telomere length after oxidative stress injury, leukocytes from healthy volunteers were extracted using Ficoll-Histopaque density gradient. The mononuclear cells layer was resuspended in cell culture medium. Oxidative stress was induced with hydrogen peroxide in cultured leukocytes. Four days later, leukocytes were treated with aripiprazole, haloperidol or clozapine for 7 days. Real-time PCR revealed that treatments with aripiprazole and haloperidol increased the telomere length by 23% and 20% in peripheral blood mononuclear cells after acute oxidative stress injury. These results suggest that haloperidol and aripiprazole can reduce the damage to telomeres induced by oxidative stress. The experiment procedure was approved by the Ethics Committee of Faculty of Medicine of the University of São Paulo (FMUSP/CAAE approval No. 52622616.8.0000.0065).

How Tim proteins differentially exploit membrane features to attain robust target sensitivity.

Immune surveillance cells such as T cells and phagocytes utilize integral plasma membrane receptors to recognize surface signatures on triggered and activated cells such as those in apoptosis. One such family of plasma membrane sensors, the transmembrane immunoglobulin and mucin domain (Tim) proteins, specifically recognize phosphatidylserine (PS) but elicit distinct immunological responses. The molecular basis for the recognition of lipid signals on target cell surfaces is not well understood. Previous results suggest that basic side chains present at the membrane interface on the Tim proteins might facilitate association with additional anionic lipids including but not necessarily limited to PS. We, therefore, performed a comparative quantitative analysis of the binding of the murine Tim1, Tim3, and Tim4, to synthetic anionic phospholipid membranes under physiologically relevant conditions. X-ray reflectivity and vesicle binding studies were used to compare the water-soluble domain of Tim3 with results previously obtained for Tim1 and Tim4. Although a calcium link was essential for all three proteins, the three homologs differed in how they balance the hydrophobic and electrostatic interactions driving membrane association. The proteins also varied in their sensing of phospholipid chain unsaturation and showed different degrees of cooperativity in their dependence on bilayer PS concentration. Surprisingly, trace amounts of anionic phosphatidic acid greatly strengthened the bilayer association of Tim3 and Tim4, but not Tim1. A novel mathematical model provided values for the binding parameters and illuminated the complex interplay among ligands. In conclusion, our results provide a quantitative description of the contrasting selectivity used by three Tim proteins in the recognition of phospholipids presented on target cell surfaces. This paradigm is generally applicable to the analysis of the binding of peripheral proteins to target membranes through the heterotropic cooperative interactions of multiple ligands.

N-acylethanolamine regulation of TLR3-induced hyperthermia and neuroinflammatory gene expression: A role for PPARα.

Increasing evidence suggests that SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is associated with increased risk of developing neurological or psychiatric conditions such as depression, anxiety or dementia. While the precise mechanism underlying this association is unknown, aberrant activation of toll-like receptor (TLR)3, a viral recognizing pattern recognition receptor, may play a key role. Synthetic cannabinoids and enhancing cannabinoid tone via inhibition of fatty acid amide hydrolase (FAAH) has been demonstrated to modulate TLR3-induced neuroimmune responses and associated sickness behaviour. However, the role of individual FAAH substrates, and the receptor mechanisms mediating these effects, are unknown. The present study examined the effects of intracerebral or systemic administration of the FAAH substrates N-oleoylethanolamide (OEA), N-palmitoylethanolamide (PEA) or the anandamide (AEA) analogue meth-AEA on hyperthermia and hypothalamic inflammatory gene expression following administration of the TLR3 agonist, and viral mimetic, poly I:C. The data demonstrate that meth-AEA does not alter TLR3-induced hyperthermia or hypothalamic inflammatory gene expression. In comparison, OEA and PEA attenuated the TLR3-induced hyperthermia, although only OEA attenuated the expression of hyperthermia-related genes (IL-1ß, iNOS, COX2 and m-PGES) in the hypothalamus. OEA, but not PEA, attenuated TLR3-induced increases in the expression of all IRF- and NFκB-related genes examined in the hypothalamus, but not in the spleen. Antagonism of PPARα prevented the OEA-induced attenuation of IRF- and NFκB-related genes in the hypothalamus following TLR3 activation but did not significantly alter temperature. PPARα agonism did not alter TLR3-induced hyperthermia or hypothalamic inflammatory gene expression. These data indicate that OEA may be the primary FAAH substrate that modulates TLR3-induced neuroinflammation and hyperthermia, effects partially mediated by PPARα.

Increasing Endocannabinoid Tone Alters Anxiety-Like and Stress Coping Behaviour in Female Rats Prenatally Exposed to Valproic Acid.

Given the sex differences evident in the prevalence of autism, there is an increased awareness of the importance of including females in autism research to determine sexual dimorphism and sex-specific treatments. Cannabinoids and endocannabinoid modulators have been proposed as potential novel treatments for autism-related symptoms; however, few studies to date have examined if these pharmacological agents elicit sex-specific effects. The aim of the present study was to use the valproic acid (VPA) model of autism to compare the behavioural responses of male and female rats and examine the effects of increasing endocannabinoid tone on the behavioural responses of VPA-exposed female rats. These data revealed that VPA-exposed male, but not female, rats exhibit reduced social responding in the three-chamber and olfactory habituation/dishabituation (OHD) test during adolescence. In comparison, VPA-exposed female, but not male, adolescent rats exhibited anxiety-like behaviour in the elevated plus maze (EPM) and open field test (OFT). In VPA-exposed female rats, increasing 2-AG levels augmented anxiety-like behaviour in the EPM and OFT, while increasing AEA levels reduced stress coping behaviour in the swim stress test. These data highlight sexual dimorphic behaviours in the VPA model and indicate that enhancing endocannabinoid levels may exacerbate negative affective behaviour in VPA-exposed females. Thus, considerations should be paid to the possible sex-specific effects of cannabinoids for the treatment of symptoms associated with autism.

The association of child maltreatment and systemic inflammation in adulthood: A systematic review.

INTRODUCTION: Child maltreatment (CM) is associated with mental and physical health disorders in adulthood. Some studies have identified elevated markers of systemic inflammation in adult survivors of CM, and inflammation may mediate the association between CM and later health problems. However, there are methodological inconsistencies in studies of the association between CM and systemic inflammation and findings are conflicting. We performed a systematic review to examine the association of CM with systemic inflammation in adults. METHODS: A pre-registered systematic review was performed following PRISMA guidelines. Medline, Embase, Scopus and PsychInfo were searched for studies of the association of CM with blood markers of inflammation in adults. Quality was assessed using the Crowe Critical Appraisal Tool. We had intended to perform a meta-analysis, but this was not possible due to variation in study design and reporting. RESULTS: Forty-four articles met criteria for inclusion in the review. The most widely reported biomarkers were C-Reactive Protein (CRP) (n = 27), interleukin-6 (IL-6) (n = 24) and Tumour Necrosis Factor-alpha (TNF-a) (n = 17). Three studies were prospective (all relating to CRP) and the remainder were retrospective. 86% of studies were based in high income countries. In the prospective studies, CM was associated with elevated CRP in adulthood. Results of retrospective studies were conflicting. Methodological issues relating to the construct of CM, methods of analysis, and accounting for confounding or mediating variables (particularly Body Mass Index) may contribute to the uncertainty in the field. CONCLUSIONS: There is some robust evidence from prospective studies that CM is associated with elevated CRP in adulthood. We have identified significant methodological inconsistencies in the literature and have proposed measures that future researchers could employ to improve consistency across studies. Further prospective, longitudinal, research using robust and comparable measures of CM with careful consideration of confounding and mediating variables is required to bring clarity to this field.

Genetic polymorphisms of the serotonin transporter are not related with depression in temporal lobe epilepsy caused by hippocampal sclerosis.

BACKGROUND: Mood disorders are the most frequent psychiatric disorders in patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS). The pathophysiological mechanisms in common between TLE and mood disorders include abnormalities in the serotonergic pathway. We aimed to evaluate the association between serotonin transporter genetic polymorphisms - 5-HTTLPR and 5-HTTVNTR - and the presence of mood disorders in patients with TLE-HS. METHODS: We evaluated 119 patients with TLE-HS, with and without psychiatric disorder; 146 patients diagnosed with major depressive disorder (MDD), and 113 healthy volunteers. Individuals were genotyped for the 5-HTTLPR and 5-HTTVNTR polymorphisms. RESULTS: No difference was observed between the TLE-HS groups, healthy controls, and MDD without epilepsy. There was a correlation between the 12-allele of the 5-HTTVNTR and the family history of patients with epilepsy with TLE-HS (p = 0.013). CONCLUSIONS: In this study conducted in two Brazilian centers, the serotonin transporter polymorphisms evaluated cannot be associated with depressive disorder in patients with TLE-HS. Still, they do have some influence over some clinical characteristics of epilepsy in TLE-HS. These data may not be reproduced in other populations with distinct ethnic characteristics.

PKC epsilon as a neonatal target to correct FXS-linked AMPA receptor translocation in the hippocampus, boost PVN oxytocin expression, and normalize adult behavior in Fmr1 knockout mice.

Fragile X Syndrome (FXS) is an inherited developmental disorder caused by the non-expression of the Fmr1 gene. FXS is associated with abnormal social and anxiety behavior that is more prominent among males. Given that oxytocin (OXT) regulates both social and anxiety behavior, we studied the effect of FXS in the hypothalamic paraventricular nucleus (PVN), the major central source of OXT. We observed a significant suppression of protein kinase C epsilon (PKCε) (34%) in the ventral hippocampal CA1 region of postnatal day-18 (P18) male Fmr1 knockout (KO) mice, which displayed social behavior deficits and hyper-anxiety in adulthood. These mice also displayed a 39% increase in cell surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) at P18 (measured by the surface level of the AMPAR subunit GluR2), thereby indicating excitation of the CA1 neurons. It is known that neuronal activation at CA1 is linked to an inhibition of the PVN neurons. As expected, these mice also displayed a 25% suppression of oxytocin+ (OXT+) cells in the PVN at P20. Stimulating PKCε during postnatal days 6-,14 (P6-14) mice using a selective activator, dicyclopropyl-linoleic acid (DCP-LA), corrected AMPAR externalization in CA1 and suppression of OXT+ cell number in PVN in a PKCε dependent manner. Most notably, neonatal DCP-LA treatment rescued social behavior deficits and hyper-anxiety, displayed by adult (≥P60) male but not female KO mice. Thus, neonatal stimulation of PKCε could be a strategy to correct endophenotypic anomalies during brain development and aberrant adult behavior of the FXS males to the wild-type levels.

Acceptability of online exercise-based interventions after breast cancer surgery: systematic review and narrative synthesis.

PURPOSE: eHealth and mHealth approaches are increasingly used to support cancer survivors. This review aimed to examine adherence, acceptability and satisfaction with Internet-based self-management programmes for post-surgical cancer rehabilitation and to identify common components of such interventions. METHODS: Nine electronic databases were searched from inception up to February 15, 2020, for relevant quantitative and qualitative studies evaluating Internet-based cancer rehabilitation interventions. Studies were required to include an exercise or physical activity-based self-management intervention and a measure of adherence, acceptability or user satisfaction with the programme. Two independent reviewers performed all data extraction and quality assessment procedures. Data were synthesized using a narrative approach. RESULTS: Six hundred ninety-six potential papers were identified and screened. Eleven met the inclusion criteria. Interventions had wide variations in levels of adherence, but the majority were reported as being acceptable to the users. Increased acceptability and user satisfaction were associated with interventions which were seen as time and cost-efficient, requiring acquisition of minimal or no new skills, which used coherent language, or which provided tailored information. The majority contained behaviour change components such as goal setting. CONCLUSIONS: Despite high levels of heterogeneity between studies, Internet-based approaches may be an acceptable method for the delivery of self-management interventions in post-surgical cancer rehabilitation. IMPLICATIONS FOR CANCER SURVIVORS: There is a need for further studies exploring factors associated with increased user engagement and usage of digital interventions in cancer rehabilitation settings. These findings should be used to help develop interventions prior to testing their effectiveness in adequately powered randomized controlled trials.

The hallmarks of childhood abuse and neglect: A systematic review.

BACKGROUND: Studies on the impacts of child maltreatment (CM) have been conducted in diverse areas. Mechanistic understanding of the complex interplay between factors is lacking. Hallmarking is an approach which identifies common factors across studies and highlights the most robust findings. OBJECTIVES: In a review of systematic reviews and meta-analyses, we addressed the following questions: 1) What are the hallmarks associated with exposure to CM across the bio-ecological spectrum? 2) What is the strength of evidence to support each hallmark? 3) What are the gaps that future research should address? METHODS: A comprehensive literature search was carried out to find relevant systematic reviews or meta-analyses. 269 articles were read in full and 178 articles, encompassing more than 6000 original papers, were included in the final synthesis. All reviews were independently rated for quality by at least 2 reviewers using AMSTAR-2. RESULTS: Of 178 review articles, 6 were rated as high quality (all meta-analyses) and 46 were rated as medium quality. Most were from high income countries. CONCLUSIONS: Based on the most commonly reported high-quality research findings we propose that the hallmarks of exposure to child maltreatment are: Increased risk of psychopathology; Increased risk of obesity; Increased risk of high- risk sexual behaviours, Increased risk of smoking; and Increased risk of child maltreatment in children with disabilities. Research gaps include a lack of focus on complexity and resilience. Little can be concluded about directions of causality or mechanisms. Adequately powered prospective studies are required to move the field forward.

Lower limb MSK injuries among school-aged rugby and football players: a systematic review.

OBJECTIVE: The objective of this systematic review was to explore the incidence of lower limb musculoskeletal (MSK) injuries sustained by rugby union, rugby league, soccer, Australian Rules and Gaelic football players under 18 years. The review sought to identify the mechanisms and types of injury sustained and to compare between sports. DESIGN: This systematic review focused on the incidence of lower limb injury in adolescent team sports that involved running and kicking a ball. A literature search of studies published prior to January 2020 was conducted using SportDiscus, Medline and PubMed databases. The Standard Quality Assessment Criteria appraisal tool was used to assess the quality of each article included in the review. Two or more authors independently reviewed all papers. RESULTS: Sixteen papers met the inclusion criteria; prospective cohort (N=14), retrospective (n=1) and longitudinal (n=1). These studies investigated injuries in rugby union and rugby league (n=10), football (soccer) (n=3), Australian Rules (n=2) and Gaelic football (n=1). There were a total of 55 882 participants, aged 7-19 years old, who reported 6525 injuries. The type, site and mechanisms of injury differed across sports. SUMMARY: Lower limb injuries were common in adolescent rugby, soccer, Gaelic football and Australian Rules football players, however these studies may not fully reflect the true injury burden where recurrent and overuse injuries have not been considered. There were differences between sports in the mechanisms, types and severity of injury.