Breast Cancer-related Lymphedema: Recent Updates on Clinical Efficacy of Therapies and Bioengineering Approaches for a Personalized Therapy.

BACKGROUND: Post-mastectomy lymphedema is a chronic progressive disease characterized by a significant reduction in quality of life and a range of complications. AIM: To this date, no single treatment method provides pathological correction of the mechanisms associated with tissue reorganization observed in later-stage breast cancer-related lymphedema (BCRL). METHODS: To define a personalized approach to the management of patients with iatrogenic lymphedema, we performed a systematic review of literature without a comprehensive meta-analysis to outline existing molecular- genetic patterns, overview current treatment methods and their efficacy, and highlight the specific tissue-associated changes in BCRL conditions and other bio-engineering approaches to develop personalized therapy. RESULTS: Our results show that several tissue-specific and pathological molecular markers may be found, yet current research does not aim to define them. CONCLUSION: As such, currently, a strong foundation for further research into molecular-genetic changes in lymphedema tissue exists, and further research should focus on finding specific targets for personalized treatment through bio-engineering approaches.

Recent Advances in Therapeutic Modalities Against Breast Cancer-Related Lymphedema: Future Epigenetic Landscape.

Background: Lymphedema is a significant postsurgical complication observed in the majority of breast cancer patients. These multifactorial etiopathogenesis have a significant role in the development of novel diagnostic/prognostic biomarkers and the development of novel therapies. This review aims to ascertain the epigenetic alterations that lead to breast cancer-related lymphedema (BCRL), multiple pathobiological events, and the underlying genetic predisposing factors, signaling cascades pertinent to the lapses in effective prognosis/diagnosis, and finally to develop a suitable therapeutic regimen. Methods and Results: We have performed a literature search in public databases such as PubMed, Medline, Google Scholar, National Library of Medicine and screened several published reports. Search words such as epigenetics to induce BCRL, prognosis/diagnosis, primary lymphedema, secondary lymphedema, genetic predisposing factors for BRCL, conventional therapies, and surgery were used in these databases. This review described several epigenetic-based predisposing factors and the pathophysiological consequences of BCRL, which affect the overall quality of life, and the interplay of these events could foster the progression of lymphedema in breast cancer survivors. Prognosis/diagnostic and therapy lapses for treating BCRL are highly challenging due to genetic and anatomical variations, alteration in the lymphatic vessel contractions, and variable expression of several factors such as vascular endothelial growth factor (VEGF)-E and vascular endothelial growth factor receptor (VEGFR) in breast cancer survivors. Conclusion: We compared the efficacy of various conventional therapies for treating BCRL as a multidisciplinary approach. Further substantial research is required to decipher underlying signaling epigenetic pathways to develop chromatin-modifying therapies pertinent to the multiple etiopathogenesis to explore the correlation between the disease pathophysiology and novel therapeutic modalities to treat BCRL.

Genomic regulatory sequences in the pathogenesis of bipolar disorder.

The lifetime prevalence of bipolar disorder is estimated to be about 2%. Epigenetics defines regulatory mechanisms that determine relatively stable patterns of gene expression by controlling all key steps, from DNA to messenger RNA to protein. This Mini Review highlights recent discoveries of modified epigenetic control resulting from genetic variants associated with bipolar disorder in genome-wide association studies. The revealed epigenetic abnormalities implicate gene transcription and post-transcriptional regulation. In the light of these discoveries, the Mini Review focuses on the genes PACS1, MCHR1, DCLK3, HAPLN4, LMAN2L, TMEM258, GNL3, LRRC57, CACNA1C, CACNA1D, and NOVA2 and their potential biological role in the pathogenesis of bipolar disorder. Molecular mechanisms under control of these genes do not translate into a unified picture and substantially more research is needed to fill the gaps in knowledge and to solve current limitations in prognosis and treatment of bipolar disorder. In conclusion, the genetic and functional studies confirm the complex nature of bipolar disorder and indicate future research directions to explore possible targeted treatment options, eventually working toward a personalized approach.

Poverty over the early life course and young adult cardio-metabolic risk.

OBJECTIVES: There is little known about whether exposure to family poverty at specific periods of the early life course independently contributes to coronary heart disease risk beyond the contribution of concurrent poverty. METHODS: Children were recruited in early pregnancy and additional survey data obtained during the pregnancy and at the 5-, 14- and 30-year follow-ups. Fasting blood samples were also obtained at the 30-year follow-up. Analyses are multinominal logistic regressions stratified by gender and with adjustments for confounding. RESULTS: For male offspring, family poverty at different stages of the early life course was not associated with measures of cardio-metabolic risk. For females early life course, poverty predicted obesity, homeostatic model assessment of insulin resistance (HOMA-IR) and total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), as well as concurrent family poverty associated with obesity, HOMA-IR, TC/HDL-C, HDL-C and increased systolic and diastolic blood pressure. CONCLUSIONS: Family poverty in the early life course independently predicts increased levels of cardio-metabolic risk of females. The primary finding, however, is that concurrent poverty is independently and strongly associated with increased cardio-metabolic risk levels in young adulthood.

Does adolescent heavier alcohol use predict young adult aggression and delinquency? Parallel analyses from four Australasian cohort studies.

While the association between heavy alcohol consumption and aggression has been well documented, the causal direction of this association, particularly at a population level, is disputed. A number of causal sequences have been proposed. First, that aggression leads to heavy alcohol use. Second, that heavy alcohol use leads to aggression. Third, that the association between alcohol use and aggression is due to confounding by (a) sociodemographic variables or (b) delinquency. We report here data from four Australasian prospective longitudinal studies of adolescents, to assess the temporal sequence of heavy drinking and aggression over the period from adolescence to young adulthood. The four cohort studies provide a total sample of 6,706 persons (Australian Temperament Project, n = 1701; Christchurch Health and Development Study, n = 931; Mater-University of Queensland Study of Pregnancy, n = 2437; Victorian Adolescent Health Cohort Study, n = 1637). We use multinomial logistic regression to determine whether early adolescent aggression predicts subsequent age of onset of heavy episodic drinking (HED), after adjustment for concurrent sociodemographic factors and delinquency. We then consider whether HED predicts subsequent aggression, after adjusting for past aggression, concurrent delinquency, and a range of confounders. There are broadly consistent findings across the four cohort studies. Early aggression strongly predicts subsequent HED. HED predicts later aggression after adjustment for prior aggression and other confounders. Policies that alter population levels of alcohol consumption are likely to impact on levels of aggression in societies where HED linked to aggression is more common.

Adverse adult consequences of different alcohol use patterns in adolescence: an integrative analysis of data to age 30 years from four Australasian cohorts.

BACKGROUND AND AIMS: Studies have linked adolescent alcohol use with adverse consequences in adulthood, yet it is unclear how strong the associations are and to what extent they may be due to confounding. Our aim was to estimate the strength of association between different patterns of adolescent drinking and longer-term psychosocial harms taking into account individual, family and peer factors. DESIGN: Participant-level data were integrated from four long-running longitudinal studies: Australian Temperament Project, Christchurch Health and Development Study, Mater Hospital and University of Queensland Study of Pregnancy and Victorian Adolescent Health Cohort Study. SETTING: Australia and New Zealand. PARTICIPANTS: Participants were assessed on multiple occasions between ages 13 and 30 years (from 1991 to 2012). Number of participants varied (up to n = 9453) by analysis. MEASUREMENTS: Three patterns of alcohol use (frequent, heavy episodic and problem drinking) were assessed prior to age 17. Thirty outcomes were assessed to age 30 spanning substance use and related problems, antisocial behaviour, sexual risk-taking, accidents, socio-economic functioning, mental health and partner relationships. FINDINGS: After covariate adjustment, weekly drinking prior to age 17 was associated with a two- to threefold increase in the odds of binge drinking [odds ratio (OR) = 2.14; 95% confidence interval (CI) = 1.57-2.90], drink driving (OR = 2.78; 95% CI = 1.84-4.19), alcohol-related problems (OR = 3.04; 95% CI = 1.90-4.84) and alcohol dependence (OR = 3.30; 95% CI = 1.69-6.47) in adulthood. Frequency of drinking accounted for a greater proportion of the rate of most adverse outcomes than the other measures of alcohol use. Associations between frequent, heavy episodic and problem drinking in adolescence and most non-alcohol outcomes were largely explained by shared risk factors for adolescent alcohol use and poor psychosocial functioning. CONCLUSIONS: Frequency of adolescent drinking predicts substance use problems in adulthood as much as, and possibly more than, heavy episodic and problem drinking independent of individual, family and peer predictors of those outcomes.

Social adversity in pregnancy and trajectories of women's depressive symptoms: A longitudinal study.

BACKGROUND: Sound evidence has linked the experience of adversity with depression. Less is known about this association over time. AIM: The aim of this study is to determine whether or not social adversity experienced by pregnant women is associated with their patterns of depressive symptoms over their reproductive life course. METHODS: Data were obtained from a cohort of women collected at their first obstetrical clinic visit of an index pregnancy (time-point 1) and at a further six time-points to 27 years following the birth. Latent Class Growth Modelling was used to estimate trajectories of women's depressive symptoms over this time period. Logistic regression modelling determined the prospective association between measures of adversity in pregnancy and 27-year postpartum depression trajectories, controlling for potential confounders. FINDINGS: Experiencing financial problems, housing problems, serious disagreements with partners and with others, and experiencing serious health problems in pregnancy were associated with membership of high and middle depression trajectories over the 27 years. Having someone close die or have a serious illness was associated with the high depression trajectory only. Younger maternal age and low family-income at first clinic visit were also associated with an increased risk of women's membership of both high and middle depression trajectories. CONCLUSIONS: Experiencing adversity during pregnancy predicts subsequent patterns of maternal depression over an extended period of women's reproductive life course. It is not clear whether women's experiences of adversity during pregnancy were causally associated with subsequent depression or whether there are other explanations of the observed association.

Cannabis use and quality of life of adolescents and young adults: findings from an Australian birth cohort.

Cannabis is generally used to enhance mood (quality of life), but it is not known whether it has this effect in the medium to longer term. Little is currently known about the temporal sequence between cannabis use and the quality of life (QOL). Data are taken from a prospective longitudinal study of pregnant women recruited at their first antenatal visit in Brisbane, Australia. Offspring data from the follow-ups with 14-year-olds and 21-year-olds are used here. Indicators of QOL, happiness, and satisfaction at 14 years are considered as predictors of subsequent cannabis use. The association between cannabis use and QOL at 21 years, adjusting for prior QOL (14 years), is also examined. Socio-demographic characteristics were included as potential confounders relevant to QOL assessments. In this cohort, lower QOL in the early teenage years predicted subsequent onset of cannabis use in young adulthood. After adjustment for socio-demographic characteristics and for QOL pre-cannabis use, participants who used cannabis more frequently had a lower QOL at the 21-years follow-up. Frequent use of cannabis does not appear to enhance the user's QOL and appears to be associated with a reduced QOL into young adulthood.

Quality of life, age of onset of alcohol use and alcohol use disorders in adolescence and young adulthood: Findings from an Australian birth cohort.

INTRODUCTION AND AIMS: Alcohol consumption among adolescents and young adults is a persistent community concern. Little is known about the short-term effects on the young adult drinker's quality of life (QOL), particularly prior to the first use of alcohol and the effect of alcohol consumption on subsequent QOL assessments. There is a need to know more about the QOL of those who decide to use alcohol in adolescence and the effect of alcohol consumption on young adult QOL. DESIGN AND METHODS: This is a prospective longitudinal study of a birth cohort. Data were taken from the 14- and 21-year follow ups. At both time points, QOL was indicated by a measure of happiness and satisfaction. Alcohol use was also measured at 14- and 21-year follow ups. At the 21-year follow up, alcohol use disorder (AUD) was assessed using the Composite International Diagnostic Interview. RESULTS: At the 14-year follow up, there was a strong association between QOL and quantity of alcohol consumed. QOL at 14 years also predicted more frequent alcohol use at 21 years of age. Poor QOL at 14 years was a strong predictor of earlier age of onset of an AUD. However, when age of onset of AUD was used to predict subsequent QOL, the associations were weak and inconsistent. DISCUSSION AND CONCLUSION: Poor QOL was associated with the early age of onset of alcohol use and AUDs. Addressing adolescent and young adult QOL may reduce the early onset of alcohol use and its potential for harm.

Does adolescent's exposure to parental intimate partner conflict and violence predict psychological distress and substance use in young adulthood? A longitudinal study.

Little is known about the extent to which parental conflict and violence differentially impact on offspring mental health and substance use. Using data from a longitudinal birth cohort study this paper examines: whether offspring exposure to parental intimate partner violence (involving physical violence which may include conflicts and/or disagreements) or parental intimate partner conflict (conflicting interactions and disagreements only) are associated with offspring depression, anxiety and substance use in early adulthood (at age 21); and whether these associations are independent of maternal background, depression and anxiety and substance use. Data (n=2,126 women and children) were taken from a large-scale Australian birth-cohort study, the Mater University of Queensland Study of Pregnancy (MUSP). IPC and IPV were measured at the 14-year follow-up. Offspring mental health outcomes--depression, anxiety and substance use--were assessed at the 21-year follow-up using the Composite International Diagnostic Interview (CIDI). Offspring of women experiencing IPV at the 14-year follow-up were more likely to manifest anxiety, nicotine, alcohol and cannabis disorders by the 21-year follow-up. These associations remained after adjustment for maternal anxiety, depression, and other potential confounders. Unlike males who experience anxiety disorders after exposure to IPV, females experience depressive and alcohol use disorders. IPV predicts offspring increased levels of substance abuse and dependence in young adulthood. Gender differences suggest differential impact.

Young adults' trajectories of Ecstasy use: a population based study.

Young adults' Ecstasy use trajectories have important implications for individual and population-level consequences of Ecstasy use, but little relevant research has been conducted. This study prospectively examines Ecstasy trajectories in a population-based sample. Data are from the Natural History Study of Drug Use, a retrospective/prospective cohort study conducted in Australia. Population screening identified a probability sample of Ecstasy users aged 19-23 years. Complete data for 30 months of follow-up, comprising 4 time intervals, were available for 297 participants (88.4% of sample). Trajectories were derived using cluster analysis based on recent Ecstasy use at each interval. Trajectory predictors were examined using a generalized ordered logit model and included Ecstasy dependence (World Mental Health Composite International Diagnostic Instrument), psychological distress (Hospital Anxiety Depression Scale), aggression (Young Adult Self Report) and contextual factors (e.g. attendance at electronic/dance music events). Three Ecstasy trajectories were identified (low, intermediate and high use). At its peak, the high-use trajectory involved 1-2 days Ecstasy use per week. Decreasing frequency of use was observed for intermediate and high-use trajectories from 12 months, independently of market factors. Intermediate and high-use trajectory membership was predicted by past Ecstasy consumption (>70 pills) and attendance at electronic/dance music events. High-use trajectory members were unlikely to have used Ecstasy for more than 3 years and tended to report consistently positive subjective effects at baseline. Given the social context and temporal course of Ecstasy use, Ecstasy trajectories might be better understood in terms of instrumental rather than addictive drug use patterns.